Updated on 2026/03/13

写真a

 
SATO Noboru
 
Organization
Academic Assembly Institute of Medicine and Dentistry IGAKU KEIRETU Professor
Faculty of Medicine School of Medicine Professor
Graduate School of Medical and Dental Sciences Biological Functions and Medical Control Professor
Title
Professor
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Degree

  • 博士（医学） ( 1993.3   筑波大学 )

Research Areas

  • Life Science / Anatomy

  • Life Science / Anatomy and histopathology of nervous system

Research History (researchmap)

  • Fukushima Medical University School of Medicine, School of medicine Department of Neuroanatomy and Embryology   Associate Professor

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Research History

  • Niigata University   Faculty of Medicine School of Medicine   Professor

    2007.4

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control   Professor

    2007.4

Education

  • University of Tsukuba   医学研究科   形態系

    - 1993

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    Country： Japan

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  • University of Tsukuba   Graduate School, Division of Medicine

    - 1993

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  • University of Tsukuba   School of Medicine

    - 1989

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  • University of Tsukuba   医学専門学群

    - 1989

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    Country： Japan

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Professional Memberships

 

Papers

  • DEVELOPMENT OF LIMB-INNERVATING MOTOR NEURONS IN CHICK AND FISH BY CONFOCAL LASER MICROSCOPY

    Noboru Sato, Kenichi Souma, Keisuke Watanabe, Hiroshi Nagashima

    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY   308   S142 - S142   2025.10

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    Language：English  

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  • Differences in ankle stabilizing function between the upper and lower fiber bundles of the anterior talofibular ligament: an anatomical study. International journal

    Mutsuaki Edama, Yuto Sekii, Kodai Sakamoto, Tomonobu Ishigaki, Hirotake Yokota, Ryo Hirabayashi, Makoto Komiya, Chie Sekine, Tomoya Takabayashi, Noboru Sato

    Scientific reports   15 ( 1 )   26126 - 26126   2025.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    This study aimed to clarify the differences in the stabilizing functions of the upper and lower fiber bundles of the anterior talofibular ligament (ATFL). Five Thiel-fixed cadavers (10 ft) were divided into an upper fiber bundle cut group (upper-cut group, 5 ft) and a lower fiber bundle cut group (lower-cut group, 5 ft). The angular conditions were set as 0-degree ankle dorsiflexion, 15-degree plantar flexion, and 30-degree plantar flexion. Anterior drawer and inversion stresses were applied using a Telos stress device at 120 N. Measurements were obtained when the upper and lower fiber bundles of the ATFL were intact (intact condition) and when either the upper or lower fiber bundle was severed (cut condition). For each group, the distance between the lateral malleolus and talus was measured using an ultrasound diagnostic device under both the intact and cut conditions and compared. Regarding anterior drawer stress, the displacement rate (%) significantly increased in both the upper- and lower-cut groups under the cut condition at 30-degree plantar flexion. Meanwhile, for the inversion stress, only the upper-cut group demonstrated a significantly increased displacement rate (%) under the cut condition at 0-degree dorsiflexion. No significant difference in either anterior drawer stress or inversion stress at any angle was observed between the two groups. Both the upper and lower fiber bundles of the ATFL may be involved in stabilizing ankle function during anterior drawer stress at 30-degree plantar flexion. In addition, the lower fiber bundle may play a role in stabilizing the ankle during inversion stress at 0-degree dorsiflexion.

    DOI： 10.1038/s41598-025-11747-8

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  • Comprehensive anatomical dissection procedure with special reference to the layer-structured facial muscles and fasciae and mouth floor. International journal

    Hisako Takami, Yuka Kobayashi, Sanako Makishi-Takano, Yuji Katsumi, Noboru Sato, Hayato Ohshima

    Journal of oral biosciences   67 ( 2 )   100660 - 100660   2025.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    OBJECTIVES: Conventional head and neck practice procedures fail to address several clinical issues. Anatomical structures were removed from the surface layers in that order, and the dissection was shifted to the deeper layer. This approach makes it difficult for medical and dental students to understand the relationships among various anatomical structures. Furthermore, it is difficult to determine the risk on the mandibular nerves and blood vessels during conventional mandible removal procedures. This study aims to develop an anatomical technique that maintains the skin, superficial facial muscles/fasciae, and mandibles, and to reveal the relationships among the bones, muscles, fasciae, blood vessels, and nerves of the face and floor of the mouth. METHODS: A total of 43 human cadavers were examined during gross anatomy courses at Niigata University from 2018 to 2022. RESULTS: Using this dissection method, students were able to understand the relationship between the facial muscles/fasciae, nerves, blood vessels, and muscles without removing the skin. Furthermore, this dissection helps surgeons to understand the risk of nerve and vascular damage during surgery as well as the efficiency of facelift methods. CONCLUSIONS: This study provided a clarity on anatomical dissection in the head and neck region and the relationship between anatomical structures from a clinical perspective.

    DOI： 10.1016/j.job.2025.100660

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  • Long-Term Clinical Landscapes of Spinal Hypertrophic Pachymeningitis With Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis. International journal

    Akihiro Nakajima, Mariko Hokari, Fumihiro Yanagimura, Etsuji Saji, Hiroshi Shimizu, Yasuko Toyoshima, Kaori Yanagawa, Musashi Arakawa, Akiko Yokoseki, Takahiro Wakasugi, Kouichirou Okamoto, Kei Watanabe, Keitaro Minato, Yutaka Otsu, Yukiko Nozawa, Daisuke Kobayashi, Kazuhiro Sanpei, Hirotoshi Kikuchi, Shunsei Hirohata, Kazuaki Awamori, Aya Nawata, Mitsunori Yamada, Hitoshi Takahashi, Masatoyo Nishizawa, Hironaka Igarashi, Noboru Sato, Akiyoshi Kakita, Osamu Onodera, Izumi Kawachi

    Neurology   104 ( 8 )   e213420   2025.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND AND OBJECTIVES: Spinal hypertrophic pachymeningitis (HP) is an extremely rare disorder characterized by the thickening of the spinal dura mater, which harbors distinct repertoires of immune cells due to the unique partitioning of the arachnoid blood-CSF barrier. The objectives were to identify the pathogenesis and therapeutic strategies for spinal HP. METHODS: This retrospective cohort study analyzed the clinical and pathologic profiles of patients with idiopathic/immune-mediated HP including spinal HP. RESULTS: Among 61 patients with idiopathic/immune-mediated HP, all 6 Japanese patients with spinal HP, with a median observation period of 88.8 months, were myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)-seropositive. The MPO-ANCA+ spinal HP cohort had the following characteristics: (1) a predominance of older women; (2) all patients were classified as having microscopic polyangiitis based on the 2022 American College of Rheumatology/European League Against Rheumatism criteria; (3) 83% of patients developed subacute/chronic myelopathy due to extramedullary spinal cord compression; (4) 50% of patients had lesion extension to the epidural compartment and vertebral column; (5) 50% of patients presented with chronic sinusitis, otitis media, or mastoiditis; (6) 33% of patients had involvement of the lower airways or kidneys; (7) a higher disease activity of the nervous system was noted based on the Birmingham Vasculitis Activity Score (BVAS), in contrast to MPO-ANCA+ cranial HP; (8) granulomatous inflammation with myofibroblasts, immune cells including granulocytes, and B-cell follicle-like structures were observed in the thickened dura mater; (9) immunotherapies (with or without surgical decompression) were effective in reducing the modified Rankin Scale score and reduced BVAS during the first active insults; (10) combined immunotherapies with glucocorticoids and cyclophosphamide/rituximab helped in reducing relapses in the long term; and (11) surgical decompression, including laminectomy and duraplasty, was necessary for compressive myelopathy. These data suggest that MPO-ANCA+ spinal HP shares common features with MPO-ANCA+ cranial HP (1, 2, 6, 8, 9, and 10), but also has unique clinical features (3, 4, 5, 7, and 11). DISCUSSION: Our findings highlight the significant pathogenic role of ANCA in spinal HP. MPO-ANCA+ spinal HP, as an organ-threatening disease, should be positioned as having unique characteristics, whether limited to the CNS or as part of a generalized form in ANCA-associated vasculitis.

    DOI： 10.1212/WNL.0000000000213420

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  • Dynamics of the suprapatellar bursa during knee joint extension

    Mutsuaki Edama, Yudai Tanaka, Tatuki Shirai, Yuki Takano, Kodai Sakamoto, Haruki Osanami, Hirotake Yokota, Ryo Hirabayashi, Tomonobu Ishigaki, Hiroshi Akuzawa, Chie Sekine, Noboru Sato

    Surgical and Radiologic Anatomy   46 ( 9 )   1387 - 1392   2024.6

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1007/s00276-024-03390-1

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    Other Link： https://link.springer.com/article/10.1007/s00276-024-03390-1/fulltext.html

  • Spatiotemporal expression patterns of R-spondins and their receptors, Lgrs, in the developing mouse telencephalon

    Keisuke Watanabe, Masao Horie, Manabu Hayatsu, Yoshikazu Mikami, Noboru Sato

    Gene Expression Patterns   49   119333 - 119333   2023.9

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.gep.2023.119333

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  • Macroscopic Anatomy of the Layered Structures of Facial Muscles and Fasciae in the Temporal-Malar-Mandible-Neck Region. International journal

    Hisako Takami, Takafumi Hayashi, Noboru Sato, Hayato Ohshima

    The Journal of craniofacial surgery   33 ( 7 )   2258 - 2266   2022.10

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    The layered structures of facial muscles and their topographical relationship with facial fasciae are still not fully understood. This study aimed to clarify the layered structures of facial muscles and fasciae in the temporal-malar-mandible-neck region. Thirty-four human cadavers were examined during gross anatomy courses at Niigata University (2017-2020). The face was composed of 3-layered (deep, middle, and superficial) fasciae and 4-layered facial muscles (first superficial, second superficial, third, and fourth muscle layers) according to the attachment of muscles and their topographical relationship with the fasciae. The deep fascia covered the temporal and masseter muscles. The parotid gland and facial nerves were enveloped in the middle fascia. The superficial fascia was continuous with the second superficial muscle layer. The connection between fourth and superficial muscles was at the malar and buccal areas, where the platysma blended with the masseter and the plural muscles blended with the buccinator. Our findings suggest that cooperation between the 4-layered structure of the facial muscles surrounding the apertures of the eyes and mouth and the superficial fascia enables humans to produce complex facial expressions. Furthermore, the spread of inflammation in the face may be owing to the layered facial muscles and fasciae, as these layered structures separate tissues into multiple compartments.

    DOI： 10.1097/SCS.0000000000008700

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  • Elbow valgus stability of the transverse bundle of the ulnar collateral ligament

    Mutsuaki Edama, Kanta Matsuzawa, Hirotake Yokota, Ryo Hirabayashi, Chie Sekine, Sae Maruyama, Noboru Sato

    BMC Musculoskeletal Disorders   22 ( 1 )   2021.10

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    Abstract

    Background

    The purpose of this study was to clarify elbow valgus stability of the transverse bundle (TB). We hypothesized that the transverse bundle is involved in elbow valgus stability.

    Methods

    Twelve elbows of six Japanese Thiel-embalmed cadavers were evaluated. The skin, subcutaneous tissue and origin of forearm flexors were removed from about 5 cm proximal to the elbow to about 5 cm distal to the elbow, and the ulnar collateral ligament was dissected (intact state). The cut state was defined as the state when the TB was cut in the middle. The joint space of the humeroulnar joint (JS) was measured in the intact state and then in the cut state. With the elbow flexed to 30°, elbow valgus stress was gradually increased to 30, 60 N using the Telos Stress Device, and the JS was measured by ultrasonography under each load condition. Paired t-testing was performed to compare the JS between the intact and cut states under each load.

    Results

    No significant difference in JS was identified between the intact and cut state at start limb position. The JS was significantly higher in the cut state than in the intact state at both 30 N and 60 N.

    Conclusion

    The findings from this study suggested that the TB may be involved in elbow valgus stability.

    DOI： 10.1186/s12891-021-04760-1

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    Other Link： https://link.springer.com/article/10.1186/s12891-021-04760-1/fulltext.html

  • Contributions of the Third and Fourth Digits and the Second and Fifth Digits of the Flexor Digitorum Superficialis Muscle to Elbow Valgus Stability

    Kanta Matsuzawa, Mutsuaki Edama, Masahiro Ikezu, Tomofumi Otsuki, Sae Maruyama, Noboru Sato

    Orthopaedic Journal of Sports Medicine   9 ( 9 )   232596712110262 - 232596712110262   2021.9

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    Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

    Background:

    Thiel cadavers have been reported to have lifelike flexibility and mechanical properties, but whether they are useful for measurement of the ulnohumeral joint space (JS) is unclear. The contributions of the third and fourth digits and the second and fifth digits of the flexor digitorum superficialis (FDS) to elbow valgus stability are also unknown.

    Purpose:

    To (1) clarify whether Thiel cadavers can be used for JS measurement on ultrasound and (2) identify the contributions to valgus stability of the third and fourth digits and the second and fifth digits of the FDS.

    Study Design:

    Descriptive laboratory study.

    Methods:

    In experiment 1 (12 elbows from human volunteers and 12 elbows from Thiel cadavers), valgus stress was increased gradually from 0 to 30 to 60 N, and the JS was compared on ultrasound between groups at each load. In experiment 2 (13 elbows from Thiel cadavers), specimens were divided into 2 groups, and the JS was measured for group 1 with the FDS intact, with tendinous insertions of the third and fourth digits cut (3/4-cut state), and with tendinous insertions of all fingers cut (all-cut state); and for group 2 at intact FDS, with tendinous insertions of the second and fifth digits cut (2/5-cut state), and at all-cut.

    Results:

    In experiment 1, the rate of change of the JS increased significantly with elbow valgus stress in both humans and Thiel cadavers, with no significant difference between groups. In experiment 2, the JS was significantly greater in the 3/4- and 2/5-cut states compared with the intact state at both 30 N (Δ<sub>3/4-cut vs intact</sub> = 0.23 mm [ P = .01]; Δ<sub>2/5-cut vs intact</sub> = 0.32 mm [ P = .02]) and 60 N (Δ<sub>3/4-cut vs intact</sub> = 0.33 mm [ P = .002]; Δ<sub>2/5-cut vs intact</sub> = 0.37 mm [ P = .04]). There was no significant difference in JS measurements between the 3/4- and 2/5-cut states at any load.

    Conclusion:

    Thiel cadavers showed JS changes similar to those of humans when valgus stress was applied. The third and fourth digits and the second and fifth digits of the FDS were involved in valgus stability, and there was no difference in their respective contributions.

    Clinical Relevance:

    This study may help in identifying function of the FDS based on structure.

    DOI： 10.1177/23259671211026247

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    Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/23259671211026247

  • Development of fin-innervating motor neurons after peripheral target removal in medaka fish Reviewed

    Akina Chiba, Kenichi Soma, Keisuke Watanabe, Hiroshi Nagashima, Noboru Sato

    Developmental Neurobiology   2020.12

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  • Novel concept for the epaxial/hypaxial boundary based on neuronal development. Reviewed International journal

    Hiroshi Nagashima, Daisuke Koga, Satoshi Kusumi, Katsuki Mukaigasa, Hiroyuki Yaginuma, Tatsuo Ushiki, Noboru Sato

    Journal of anatomy   237 ( 3 )   427 - 438   2020.8

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    Trunk muscles in vertebrates are classified as either dorsal epaxial or ventral hypaxial muscles. Epaxial and hypaxial muscles are defined as muscles innervated by the dorsal and ventral rami of spinal nerves, respectively. Each cluster of spinal motor neurons passing through dorsal rami innervates epaxial muscles, whereas clusters traveling on the ventral rami innervate hypaxial muscles. Herein, we show that some motor neurons exhibiting molecular profiles for epaxial muscles follow a path in the ventral rami. Dorsal deep-shoulder muscles and some body wall muscles are defined as hypaxial due to innervation via the ventral rami, but a part of these ventral rami has the molecular profile of motor neurons that innervate epaxial muscles. Thus, the epaxial and hypaxial boundary cannot be determined simply by the ramification pattern of spinal nerves. We propose that, although muscle innervation occurs via the ventral rami, dorsal deep-shoulder muscles and some body wall muscles represent an intermediate group that lies between epaxial and hypaxial muscles.

    DOI： 10.1111/joa.13219

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  • The fornix acts as a permissive corridor for septal neuron migration beyond the diencephalic-telencephalic boundary. Reviewed International journal

    Keisuke Watanabe, Hirohide Takebayashi, Noboru Sato

    Scientific reports   10 ( 1 )   8315 - 8315   2020.5

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    Neuronal migration is essential for constructing functional neural networks. Two posterior septal (PS) nuclei, the triangular septal nucleus and bed nuclei of the anterior commissure, are involved in fear and anxiety. During development, glutamatergic PS neurons undergo long-distance rostrodorsal migration from the thalamic eminence (TE) of the diencephalon, then settle in the caudalmost telencephalon. However, the developmental behavior of PS neurons and the guidance structures facilitating their migration remain unknown. We previously demonstrated the migration of PS neurons along the fornix, a major efferent pathway from the hippocampal formation. Here, we show that the postcommissural fornix is essential for PS neuron migration which is largely confined to its axonal tract, which grows in the opposite direction as PS neuron migration. Fornical axons reach the TE prior to initiation of PS neuron rostrodorsal migration. Ectopic expression of Semaphorin 3 A in the dorsomedial cortex resulted in defective fornix formation. Furthermore, loss of the postcommissural fornix stalled PS neuron migration resulting in abnormal accumulation near their origin. This suggests that PS neurons utilize the postcommissural fornix as a permissive corridor during migration beyond the diencephalic-telencephalic boundary. This axonal support is essential for the functional organization of the heterogeneous septal nuclear complex.

    DOI： 10.1038/s41598-020-65284-7

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  • Development of a mouse nerve-transfer model for brachial plexus injury. Reviewed

    Hanako Wakatsuki, Minoru Shibata, Ken Matsuda, Noboru Sato

    Biomedical research (Tokyo, Japan)   40 ( 3 )   115 - 123   2019

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    Nerve transfer involves the use of a portion of a healthy nerve to repair an injured nerve, and the process has been used to alleviate traumatic brachial plexus injuries in humans. Study of the neural mechanisms that occur during nerve transfer, however, requires the establishment of reliable experimental models. In this study, we developed an ulnar-musculocutaneous nerve-transfer model wherein the biceps muscle of a mouse was re-innervated using a donor ulnar nerve. Similar muscle action potentials were detected in both the end-to-end suture of the transected nerve (correctrepair) group and the ulnar-musculocutaneous nerve-transfer group. Also, re-innervated acetylcholine receptor (AChR) clusters and muscle spindles were observed in both procedures. There were fewer re-innervated AChR clusters in the nerve transfer group than in the correct repair group at 4 weeks, but the numbers were equal at 24 weeks following surgery. Thus, our ulnar-musculocutaneous nerve-transfer model allowed physiological and morphological evaluation for re-innervation process in mice and revealed the delay of this process during nerve transfer procedure. This model will provide great opportunities to study regeneration, re-innervation, and functional recovery induced via nerve transfer procedures.

    DOI： 10.2220/biomedres.40.115

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  • Diencephalic progenitors contribute to the posterior septum through rostral migration along the hippocampal axonal pathway. Reviewed International journal

    Keisuke Watanabe, Koichiro Irie, Carina Hanashima, Hirohide Takebayashi, Noboru Sato

    Scientific reports   8 ( 1 )   11728 - 11728   2018.8

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    DOI： 10.1038/s41598-018-30020-9

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  • Motor neurons with limb-innervating character in the cervical spinal cord are sculpted by apoptosis based on the Hox code in chick embryo. Reviewed International journal

    Katsuki Mukaigasa, Chie Sakuma, Tomoaki Okada, Shunsaku Homma, Takako Shimada, Keiji Nishiyama, Noboru Sato, Hiroyuki Yaginuma

    Development (Cambridge, England)   144 ( 24 )   4645 - 4657   2017.12

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    DOI： 10.1242/dev.158873

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  • Developmental origin of the clavicle, and its implications for the evolution of the neck and the paired appendages in vertebrates. Reviewed International journal

    Hiroshi Nagashima, Fumiaki Sugahara, Keisuke Watanabe, Masahiro Shibata, Akina Chiba, Noboru Sato

    Journal of anatomy   229 ( 4 )   536 - 48   2016.10

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    DOI： 10.1111/joa.12502

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  • A specific tripeptidyl substrate for tripeptidyl peptidase activity is effectively hydrolyzed by alanyl aminopeptidase/aminopeptidase N/CD13 in the rat kidney

    Masahiro Shibata, Masato Koike, Satoshi Kusumi, Noboru Sato, Yasuo Uchiyama

    Archives of Histology and Cytology   76 ( 1 )   1 - 8   2016.3

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    DOI： 10.1679/aohc.76.1

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  • Evidence from cyclostomes for complex regionalization of the ancestral vertebrate brain. Reviewed International journal

    Fumiaki Sugahara, Juan Pascual-Anaya, Yasuhiro Oisi, Shigehiro Kuraku, Shin-ichi Aota, Noritaka Adachi, Wataru Takagi, Tamami Hirai, Noboru Sato, Yasunori Murakami, Shigeru Kuratani

    Nature   531 ( 7592 )   97 - 100   2016.3

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    DOI： 10.1038/nature16518

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  • Endoplasmic Reticulum-Localized Transmembrane Protein Dpy19L1 Is Required for Neurite Outgrowth. Reviewed International journal

    Keisuke Watanabe, Norihisa Bizen, Noboru Sato, Hirohide Takebayashi

    PloS one   11 ( 12 )   e0167985   2016

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    DOI： 10.1371/journal.pone.0167985

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  • On the homology of the shoulder girdle in turtles. Reviewed International journal

    Hiroshi Nagashima, Fumiaki Sugahara, Masaki Takechi, Noboru Sato, Shigeru Kuratani

    Journal of experimental zoology. Part B, Molecular and developmental evolution   324 ( 3 )   244 - 54   2015.5

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    DOI： 10.1002/jez.b.22584

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  • On the homology of the shoulder girdle in turtles. Reviewed

    Nagashima, H, Sugahara, F, Takechi, M, Sato, N, Kuratani, S

    J. Exp. Zool. B Mol. Dev. Evol.   324 ( 3 )   244 - 254   2015.5

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    The shoulder girdle in turtles is encapsulated in the shell and has a triradiate morphology. Due to its unique configuration among amniotes, many theories have been proposed about the skeletal identities of the projections for the past two centuries. Although the dorsal ramus represents the scapular blade, the ventral two rami remain uncertain. In particular, the ventrorostral process has been compared to a clavicle, an acromion, and a procoracoid based on its morphology, its connectivity to the rest of the skeleton and to muscles, as well as with its ossification center, cell lineage, and gene expression. In making these comparisons, the shoulder girdle skeleton of anurans has often been used as a reference. This review traces the history of the debate on the homology of the shoulder girdle in turtles. And based on the integrative aspects of developmental biology, comparative morphology, and paleontology, we suggest acromion and procoracoid identities for the two ventral processes.

    DOI： 10.1002/jez.b.22584

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  • Comparative study of the shell development of hard- and soft-shelled turtles. Reviewed International journal

    Hiroshi Nagashima, Masahiro Shibata, Mari Taniguchi, Shintaro Ueno, Naoki Kamezaki, Noboru Sato

    Journal of anatomy   225 ( 1 )   60 - 70   2014.7

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    DOI： 10.1111/joa.12189

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  • Origin of the unique morphology of the shoulder girdle in turtles. Reviewed International journal

    Hiroshi Nagashima, Tatsuya Hirasawa, Fumiaki Sugahara, Masaki Takechi, Ryo Usuda, Noboru Sato, Shigeru Kuratani

    Journal of anatomy   223 ( 6 )   547 - 56   2013.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/joa.12116

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  • Elucidation of target muscle and detailed development of dorsal motor neurons in chick embryo spinal cord. Reviewed International journal

    Nobumi Kobayashi, Shunsaku Homma, Tomoaki Okada, Tomoyuki Masuda, Noboru Sato, Keiji Nishiyama, Chie Sakuma, Takako Shimada, Hiroyuki Yaginuma

    The Journal of comparative neurology   521 ( 13 )   2987 - 3002   2013.9

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    DOI： 10.1002/cne.23326

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  • Neurogenin2 expression together with NeuroM regulates GDNF family neurotrophic factor receptor α1 (GFRα1) expression in the embryonic spinal cord. Reviewed International journal

    Takako Shimada, Hiroyuki Yaginuma, Noboru Sato, Shunsaku Homma

    Developmental biology   370 ( 2 )   250 - 63   2012.10

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    DOI： 10.1016/j.ydbio.2012.08.002

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  • Bilateral, asymmetric anomalies of the anterior bellies of digastric muscles. Reviewed

    Yosuke Yamazaki, Masahiro Shibata, Tatsuo Ushiki, Keitaro Isokawa, Noboru Sato

    Journal of oral science   53 ( 4 )   523 - 7   2011.12

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    Bilateral, asymmetric anomalies of the anterior bellies of digastric muscles were observed during dissection of the submental region. Specifically, four extra muscle bundles were found between the anterior bellies of the digastric muscle. Although anomalies of the anterior bellies of digastric muscles are often observed, this complicated pattern of digastric anomalies has not been previously reported. Our findings and previous observations illustrate the morphogenetic complexity of the anterior belly of the digastric muscle derived from the first pharyngeal arch, which gives rise to jaw musculature such as the mylohyoid muscle.

    DOI： 10.2334/josnusd.53.523

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  • Intrasulcal Electrocorticography in Macaque Monkeys with Minimally Invasive Neurosurgical Protocols

    Takeshi Matsuo, Keisuke Kawasaki, Takahiro Osada, Hirohito Sawahata, Takafumi Suzuki, Masahiro Shibata, Naohisa Miyakawa, Kiyoshi Nakahara, Atsuhiko Iijima, Noboru Sato, Kensuke Kawai, Nobuhito Saito, Isao Hasegawa

    Frontiers in Systems Neuroscience   5   2011

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    Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

    DOI： 10.3389/fnsys.2011.00034

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  • Intrasulcal electrocorticography in macaque monkeys Reviewed

    Keisuke Kawasaki, Takeshi Matsuo, Takahiro Osada, Hirohito Sawahata, Takafumi Suzuki, Masahiro Shibata, Naohisa Miyakawa, Kiyoshi Nakahara, Noboru Sato, Kensuke Kawai, Nobuhito Saito, Isao Hasegawa

    NEUROSCIENCE RESEARCH   71   E413 - E414   2011

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  • ISLR2 expression during the period of naturally occurring cell death in the embryonic nervous system Reviewed

    Shunsaku Homma, Takako Shimada, Masahiro Shibata, Noboru Sato, Yasuo Uchiyama, Hiroyuki Yaginuma

    NEUROSCIENCE RESEARCH   68   E257 - E257   2010

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  • Conditional RNA interference using a combination of Cre-loxP system and Tol2 transposition is a useful tool for the developmental studies in the chick Reviewed

    Masahiro Shibata, Kenjiro Ito, Noboru Sato

    NEUROSCIENCE RESEARCH   68   E372 - E372   2010

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  • Efficient gene transfer to developing chick astrocytes by Tol2 transposition Reviewed

    Masahiro Shibata, Ryosuke Inoue, Noboru Sato

    MECHANISMS OF DEVELOPMENT   126   S319 - S320   2009.8

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    Masahiro Shibata, Ryosuke Inoue, Noboru Sato

    NEUROSCIENCE RESEARCH   65   S88 - S88   2009

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  • Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo

    N Sato, C Sakuma, Y Sato, TW Gould, RW Oppenheim, H Yaginuma

    CELL DEATH AND DIFFERENTIATION   13 ( 3 )   435 - 445   2006.3

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    DOI： 10.1038/sj.cdd.4401760

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  • Early motoneuron death in the cervical spinal cord of the avian embryo occurs in the subgroup of motoneurons that correspond to the motoneurons innervating intercostal muscles Reviewed

    Hiroyuki Yaginuma, Nobumi Kobayashi, Shunsaku Homma, Noboru Sato, Takako Shimada, Chie Sakuma

    NEUROSCIENCE RESEARCH   55   S120 - S120   2006

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  • Spatial and temporal regulation of gene transfer in the chicken embryo Reviewed

    Noboru Sato, Chie Sakuma, Hiroyuki Yaginuma

    NEUROSCIENCE RESEARCH   55   S106 - S106   2006

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  • Gene delivery into the chicken embryo by using replication-competent retroviral vectors. Reviewed

    Noboru Sato

    Fukushima journal of medical science   50 ( 2 )   37 - 46   2004.12

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    Rous sarcoma virus (RSV)-derived retroviral vectors have allowed for efficient gene transfer into the chicken embryo which is a classical model for studying vertebrate development. Current evidence reveals that this method can be used for regionally restricted expression, inducible expression, and for interfering with endogenous gene function, suggesting that gain-of-function and loss-of-function strategies for specific genes can be achieved spatially and temporally in the avian embryo. Thus, retroviral-mediated gene transfer into the chicken embryo coupled with a wide variety of strategies is now an important tool to address specific biological questions in the vertebrate.

    DOI： 10.5387/fms.50.37

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  • Bcl-2 rescues motoneurons from early cell death in the cervical spinal cord of the chicken embryo. Reviewed International journal

    Noboru Sato, Chie Sakuma, Hiromi Kato, Carolanne E Milligan, Ronald W Oppenheim, Hiroyuki Yaginuma

    Journal of neurobiology   53 ( 3 )   381 - 90   2002.11

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    DOI： 10.1002/neu.10108

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  • Regulated gene expression in the chicken embryo by using replication-competent retroviral vectors. Reviewed International journal

    Noboru Sato, Kenji Matsuda, Chie Sakuma, Douglas N Foster, Ronald W Oppenheim, Hiroyuki Yaginuma

    Journal of virology   76 ( 4 )   1980 - 5   2002.2

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    DOI： 10.1128/JVI.76.4.1980-1985.2002

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  • Roles of Caspases in the programmed cell death of motoneurons in vivo Reviewed

    H Yaginuma, N Sato, S Homma, RW Oppenheim

    ARCHIVES OF HISTOLOGY AND CYTOLOGY   64 ( 5 )   461 - 474   2001.12

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  • Selective localization of Bcl-2 to the inner mitochondrial and smooth endoplasmic reticulum membranes in mammalian cells Reviewed

    T Gotow, M Shibata, S Kanamori, O Tokuno, Y Ohsawa, N Sato, K Isahara, Y Yayoi, T Watanabe, JF Leterrier, M Linden, E Kominami, Y Uchiyama

    CELL DEATH AND DIFFERENTIATION   7 ( 7 )   666 - 674   2000.7

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    DOI： 10.1038/sj.cdd.4400694

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  • Novel biphasic effect of pyrrolidine dithiocarbamate on neuronal cell viability is mediated by the differential regulation of intracellular zinc and copper ion levels, NF-kappa B, and MAP kinases Reviewed

    KC Chung, JH Park, CH Kim, HW Lee, N Sato, Y Uchiyama, YS Ahn

    JOURNAL OF NEUROSCIENCE RESEARCH   59 ( 1 )   117 - 125   2000.1

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    DOI： 10.1002/(SICI)1097-4547(20000101)59:1<117::AID-JNR14>3.0.CO;2-Q

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  • Regulation of a novel pathway for cell death by lysosomal aspartic and cysteine proteinases Reviewed

    K Isahara, Y Ohsawa, S Kanamori, M Shibata, S Waguri, N Sato, T Gotow, T Watanabe, T Momoi, K Urase, E Kominami, Y Uchiyama

    NEUROSCIENCE   91 ( 1 )   233 - 249   1999

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    DOI： 10.1016/S0306-4522(98)00566-1

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  • A novel strategy for introducing exogenous Bcl-2 into neuronal cells: The Cre/loxP system-mediated activation of Bcl-2 for preventing programmed cell death using recombinant adenoviruses

    N Sato, SW Wang, L Li, K Okabe, M Hashimoto, H Yaginuma, K Mikoshiba, Y Uchiyama, T Uetsuki, K Yoshikawa, CE Milligan, RW Oppenheim

    MOLECULAR AND CELLULAR NEUROSCIENCE   12 ( 1-2 )   65 - 78   1998.9

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    DOI： 10.1006/mcne.1998.0703

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  • Suppression of lysosomal proteolysis at three different steps in regenerating rat liver Reviewed

    Watanabe K, Ishidoh K, Ueno T, Sato N, Kominami E

    Journal of Biochemistry   124 ( 5 )   947 - 956   1998

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    Decreased lysosomal proteolysis in regenerating liver after 70% hepatectomy was analyzed. The activities of cathepsins B and L increased transiently 4 h after hepatectomy, began to decrease gradually reaching about 30% of the control level at 24 h, then returned to near control level after 7 days. Immunoblot and RNA blot analyses confirmed that the changes in cathepsin activities coincided with changes in protein levels and mRNA levels. In parallel with the changes in cathepsins, we found that the amounts of LGP120, LGP110, and LGP85, three integral lysosomal membrane proteins, declined significantly after hepatectomy, suggesting that the lysosomal levels are also diminished in regenerating liver. We isolated dextran-loaded lysosomes and found that the protein content and marker enzyme activities of dextran-loaded lysosomes from partially hepatectomized livers are lower by 50 and 40%, respectively, compared with control livers. This indicates that there is a significant reduction in the cellular lysosomal level in regenerating liver. In addition, we used a sensitive biochemical assay to quantify leupeptin-induced autolysosomes and found that the autophagic activity is markedly suppressed in regenerating liver as compared with normal liver. Thus, the suppression of lysosomal proteolysis in regenerating liver is attained through three steps, <i>i.e.</i>, decreased biosynthesis of cathepsins, decreased lysosomal biogenesis, and decreased cellular autophagy.

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  • Cloning and expression of the cDNA encoding rat caspase-2

    Noboru Sato, Carolanne E. Milligan, Yasuo Uchiyama, Ronald W. Oppenheim

    Gene   202 ( 1-2 )   127 - 132   1997.11

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    DOI： 10.1016/S0378-1119(97)00463-0

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  • Lysosomal cysteine and aspartic proteinases and ubiquitin in rat and human urinary bladder epithelium Reviewed

    H Tokunaga, S Waguri, N Sato, Y Ohsawa, Y Banya, E Kominami, Y Uchiyama

    ARCHIVES OF HISTOLOGY AND CYTOLOGY   59 ( 3 )   249 - 260   1996.8

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    DOI： 10.1679/aohc.59.249

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  • Participation of cathepsins B, H, and L in perikaryal condensation of Ca1 pyramidal neurons undergoing apoptosis after brief ischemia Reviewed

    T Nitatori, N Sato, E Kominami, Y Uchiyama

    INTRACELLULAR PROTEIN CATABOLISM   389   177 - 185   1996

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  • CYSTEINE PROTEINASES IN GH(4)C(1) CELLS, A RAT PITUITARY-TUMOR CELL-LINE, ARE SECRETED BY THE CONSTITUTIVE AND REGULATED SECRETORY PATHWAYS Reviewed

    S WAGURI, N SATO, T WATANABE, K ISHIDOH, E KOMINAMI, K SATO, Y UCHIYAMA

    EUROPEAN JOURNAL OF CELL BIOLOGY   67 ( 4 )   308 - 318   1995.8

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  • THE FATE OF EFFETE EPITHELIAL-CELLS AT THE VILLUS TIPS OF THE HUMAN SMALL-INTESTINE Reviewed

    T SHIBAHARA, N SATO, S WAGURI, T IWANAGA, A NAKAHARA, H FUKUTOMI, Y UCHIYAMA

    ARCHIVES OF HISTOLOGY AND CYTOLOGY   58 ( 2 )   205 - 219   1995.6

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    DOI： 10.1679/aohc.58.205

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  • APOPTOSIS AND HETEROPHAGY OF MEDIAL EDGE EPITHELIAL-CELLS OF THE SECONDARY PALATINE SHELVES DURING FUSION Reviewed

    K TANIGUCHI, N SATO, Y UCHIYAMA

    ARCHIVES OF HISTOLOGY AND CYTOLOGY   58 ( 2 )   191 - 203   1995.6

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    DOI： 10.1679/aohc.58.191

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  • DELAYED NEURONAL DEATH IN THE CA1 PYRAMIDAL CELL LAYER OF THE GERBIL HIPPOCAMPUS FOLLOWING TRANSIENT ISCHEMIA IS APOPTOSIS Reviewed

    T NITATORI, N SATO, S WAGURI, Y KARASAWA, H ARAKI, K SHIBANAI, E KOMINAMI, Y UCHIYAMA

    JOURNAL OF NEUROSCIENCE   15 ( 2 )   1001 - 1011   1995.2

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  • NEURONAL DIFFERENTIATION OF PC12 CELLS AS A RESULT OF PREVENTION OF CELL-DEATH BY BCL-2

    N SATO, K HOTTA, S WAGURI, T NITATORI, K TOHYAMA, Y TSUJIMOTO, Y UCHIYAMA

    JOURNAL OF NEUROBIOLOGY   25 ( 10 )   1227 - 1234   1994.10

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    DOI： 10.1002/neu.480251005

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  • Cell and tissue distribution of lysosomal cysteine proteinases, cathepsins B, H, and L, and their biological roles Reviewed

    Uchiyama Y, Waguri S, Sato N, Watanabe T, Ishido K, Kominami E

    Acta Histochemica et Cytochemica   27 ( 4 )   287 - 308   1994

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    Cathepsins B, H, and L, representative lysosomal cysteine proteinases, have been shown to be involved in the degradation of proteins, generation of bioactive proteins, antigen processing, etc. Recent biochemical as well as Immunohisto/cytochemical studies have demonstrated that these enzymes are transferred from the trans Golgi network to lysosomes of cells, and in some cases, to secretory granules of certain endocrine cells, or they are secreted from cells. Localization of these enzymes in lysosomes differs depending on cell types even in the same tissues, suggesting that expression of these enzymes is regulated corresponding to cell specialization. Cathepsins B and H are localized in secretory granules of some peptide hormone-producing cells; particularly, cathepsin B is co-localized with renin in various endocrine cells producing active renin, indicating that cathepsin B is a major candidate of the renin converting enzyme. Moreover, these cysteine proteinases are secreted as their pro- or active forms from various tissue cells. In the resorption lacuna facing osteoclasts, secreted cathepsin L has been suggested to play a major role in the degradation of organic bone constituents, particularly collagen. Thus cathepsins B, H, and L act as biomodulators in various cells and tissues. In the present review, we introduce the precise localization of cathepsins B, H, and L and discuss their possible roles in cells and tissues.

    DOI： 10.1267/ahc.27.287

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  • COEXISTENCE OF RENIN AND CATHEPSIN-B IN SECRETORY GRANULES OF GRANULAR DUCT CELLS IN MALE-MOUSE SUBMANDIBULAR-GLAND Reviewed

    K SANO, S WAGURI, N SATO, E KOMINAMI, Y UCHIYAMA

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   41 ( 3 )   433 - 438   1993.3

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    DOI： 10.1177/41.3.8429206

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  • STRUCTURAL ORGANIZATION OF THE GENE ENCODING RAT CYSTATIN-BETA

    N SATO, K ISHIDOH, Y UCHIYAMA, E KOMINAMI

    GENE   114 ( 2 )   257 - 260   1992.5

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  • IMMUNOCYTOCHEMICAL LOCALIZATION OF CATHEPSIN-B IN RAT ANTERIOR-PITUITARY ENDOCRINE-CELLS, WITH SPECIAL REFERENCE TO ITS COLOCALIZATION WITH RENIN AND PRORENIN IN GONADOTROPHS Reviewed

    Y UCHIYAMA, M NAKAJIMA, T WATANABE, S WAGURI, N SATO, M YAMAMOTO, Y HASHIZUME, E KOMINAMI

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   39 ( 9 )   1199 - 1205   1991.9

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    DOI： 10.1177/39.9.1918937

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  • CYSTEINE PROTEINASES IN BRONCHOALVEOLAR EPITHELIAL-CELLS AND LAVAGE FLUID OF RAT LUNG Reviewed

    Y ISHII, Y HASHIZUME, T WATANABE, S WAGURI, N SATO, M YAMAMOTO, S HASEGAWA, E KOMINAMI, Y UCHIYAMA

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   39 ( 4 )   461 - 468   1991.4

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    DOI： 10.1177/39.4.2005374

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  • Molecular cloning of cDNA for rat cathepsin C: Cathepsin C, A cysteine proteinase with an extremely long propeptide Reviewed

    Ishidoh K, Muno D, Sato N, Kominami E

    Journal of Biological Chemistry   266 ( 25 )   16312 - 16317   1991

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  • MOLECULAR-CLONING AND SEQUENCING OF CDNA FOR RAT CYSTATIN-BETA

    N SATO, K ISHIDOH, Y UCHIYAMA, E KOMINAMI

    NUCLEIC ACIDS RESEARCH   18 ( 22 )   6698 - 6698   1990.11

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  • IMMUNOCYTOCHEMICAL LOCALIZATION OF CATHEPSIN-B AND CATHEPSIN-H IN CORTICOTROPHS AND MELANOTROPHS OF RAT PITUITARY-GLAND Reviewed

    Y UCHIYAMA, M NAKAJIMA, D MUNO, T WATANABE, Y ISHII, S WAGURI, N SATO, E KOMINAMI

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   38 ( 5 )   633 - 639   1990.5

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    DOI： 10.1177/38.5.2159033

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Books

  • 培養細胞への遺伝子導入

    学際企画・組織細胞化学2000  2000 

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MISC

  • 神経系のプログラム細胞死期におけるISLR2の発現様式(ISLR2 expression during the period of naturally occurring cell death in the embryonic nervous system)

    本間 俊作, 島田 孝子, 柴田 昌宏, 佐藤 昇, 内山 安男, 八木沼 洋行

    神経化学   49 ( 2-3 )   631 - 631   2010.8

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  • Regulated gene expression in the chicken embryo by using replication-competent retroviral vectors

    N Sato, K Matsuda, C Sakuma, DN Foster, RW Oppenheim, H Yaginuma

    JOURNAL OF VIROLOGY   76 ( 4 )   1980 - 1985   2002.2

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  • Bcl-2の抗アポトーシス作用発現とミトコンドリア内膜への局在

    金森 市朗, 後藤 隆洋, 柴田 昌宏, 井佐原 京子, 大沢 良之, 佐藤 昇, 渡部 剛, 内山 安男

    神経化学   37 ( 3 )   370 - 370   1998.9

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Presentations

  • 神経系形成におけるRhoシグナル伝達の重要性

    第112回日本解剖学会総会・全国学術集会  2007 

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  • Distinct susceptibility of developing neurons to death after Bax overexpression in the chicken embryo

    36th Annual Meeting,Society for neuroscience  2006 

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  • Spatial and temporal regulation of gene transfer in the chicken embryo.

    2006 

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  • Distinct susceptibility of developing neurons to death after Bax overexpression in the chicken embryo

    36th Annual Meeting,Society for neuroscience  2006 

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  • ニワトリ胚での空間的・時間的な遺伝子発現の制御

    日本解剖学会  2006 

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  • Spatial and temporal regulation of gene transfer in the chicken embryo.

    2006 

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Research Projects

  • Establishment of a non-invasive evaluation method for Achilles tendon twisted structure and development of injury prevention methods focusing on tendon structure and characteristics

    Grant number：23K27948

    2024.4 - 2027.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\7800000 （ Direct Cost: \6000000 、 Indirect Cost：\1800000 ）

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  • Establishment of a non-invasive evaluation method for Achilles tendon twisted structure and development of injury prevention methods focusing on tendon structure and characteristics

    Grant number：23H03258

    2023.4 - 2027.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\18980000 （ Direct Cost: \14600000 、 Indirect Cost：\4380000 ）

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  • Establishment of morphological and histological basis of fascial structure and development of new exercise therapy

    Grant number：22K19739

    2022.6 - 2025.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Challenging Research (Exploratory)

    Awarding organization：Japan Society for the Promotion of Science

    Edama Mutsuaki

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    Grant amount：\6370000 （ Direct Cost: \4900000 、 Indirect Cost：\1470000 ）

    This study aimed to anatomically clarify regional differences in fascial structure and the distribution patterns of nociceptive nerve fibers. Gross anatomical analysis revealed that fascial morphology differs by region. In areas such as the trapezius and gluteus maximus muscles, which are commonly involved in conditions like shoulder stiffness and low back pain, the superficial fascia was absent, and the epimysium and perimysium were strongly connected to subcutaneous collagen and elastic fibers. In the tibialis anterior fascia, the distribution of peripherin-immunoreactive (Peripherin-ir) nerve fibers varied by region. Quantitative analysis showed significantly higher Peripherin-positive fiber density in the distal portion compared to the proximal and intermediate portions. These findings suggest that morphological characteristics of the fascia are closely related to the regional density of nociceptive fibers and may contribute to the pathophysiology of myofascial pain.

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  • 末梢標的とその支配神経形成についての定説の再考

    Grant number：22K06807

    2022.4 - 2025.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    佐藤 昇

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

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  • Development of a mouse nerve-transfer model for brachial plexus injury

    Grant number：16K20353

    2016.4 - 2019.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Young Scientists (B)

    Awarding organization：Japan Society for the Promotion of Science

    Hanako Wakatsuki, SATO Noboru, SHIBATA Minoru, MATSUDA Ken

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    To establish a mouse model for ulnar-musculocutaneous nerve transfer, we initially checked the anatomy of the mouse brachial plexus. the musculocutaneous nerve contains motor fibers from the ventral horn of C5 to C7 and sensory fibers from the spinal ganglions of C5 to C7 (Fig. 2A). Conversely, the ulnar nerve originated at the C8 and Th1 levels of the cord.
    We established an ulnar-musculocutaneous nerve-transfer model for the treatment of brachial plexus injury in mice. In this model, donor ulnar nerve regeneration and re-innervation was electrophysiologically and morphologically confirmed.This model should provide great opportunities to study regeneration, re-innervation and functional recovery induced by nerve transfer procedures, which could lead to new therapeutic methods for function recovery.

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  • Study of nerve plasticity after nerve corssing using three dementional imaging reconstruction

    Grant number：25293362

    2013.4 - 2017.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    Shibata Minoru, SATO Noboru, USHIKI Tatsuo, SHIBUKI Katsuei

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    Grant amount：\17940000 （ Direct Cost: \13800000 、 Indirect Cost：\4140000 ）

    Nerve crossing recently become useful nerve repairing method, however, this procedure should theoretically invites unusefull missreinnervation. We anticipated unknown nerve purposeful neural plasticity worked after nerve crossing. We established nerve crossing technique in the extremely small peripheral nerve in the upper arm to allow hole mount brachial plexus observation. Retrograding tracing of ulnar and musculocutaneous nerve revealed spinal neuron innervation and there was almost no overlapping innervation between ulnar and musculocutaneous nerve. It was found that after crossing of proximal ulna and distal musculocutaneous nerve retrograde tracing from distal to the crossing site identified participation of musculocutaneous nerve innervating neuron tracing in addition to the ulnar innervating neurons. Electrophysiological study demostrated useful reinnervation by this type of crossing procedure. Observation of whole mounting brachial plexus is proceeding.

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  • Gene transfer to the chick during later embryonic development using transposon

    Grant number：22590188

    2010 - 2012

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    SATO Noboru, SIBATA Masahiro

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    This study is planned to clear how transposon-mediated gene transfer does work in the chicken embryo during the later period of development. It is shown that transposon-mediated gene transfer allows efficient delivery of the trangene into the chicken embryo until the later period of development. It is also suggested that the gene expression cassette should be precisely constructed to introduce the transgene into the specific cell and tissue.

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  • Study of temporal and spatial labeling of developing niotoneurons

    Grant number：19590192

    2007 - 2008

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    SATOU Noboru, MIYAWAKI Makoto, SUZUKI Ryou

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • Analysis of the mechanisms of cell death that involves a specific subgroup of motoneurons.

    Grant number：18500266

    2006 - 2007

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YAGINUMA Hiroyuki, HOMMA Shunsaku, MASUDA Tomoyuki

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    Grant amount：\3890000 （ Direct Cost: \3500000 、 Indirect Cost：\390000 ）

    To determine the identity of the dying motoneurons (MNs) undergoing programmed cell death (PCD) at relatively early stages (E4-E5 in the chick embryo) and only in the non-limb innervating cervical spinal cord, we examined expression of subgroup-specific MN markers (Isl1, Is12, Lim3, MNR2 and Foxpl) in the dying MNs. PCD occurs only in a subgroup of MNs that express Isl1, Isl2, MNR2 and FoxPl but that lack Lim3 expression. This Lim3-negative (Lim3) MN subgroup appears as a distinct subpopulation in the dorsolateral region of the ventral horn by E4 after losing Lim3 expression and they are no longer observed by E5. However, following the rescue of MNs by Bc12 overexpression, Lim3- persisted at least until E5-5.5. When Lim3 was overexpressed on one side of the spinal cord, the number of dying MNs was markedly decreased at E4.5 and the number of surviving healthy MNs was increased after the period of cell death (E5.5). These results suggest that the downregulation of Lim3 is involved in the specification of the cell death fate of early dying cervical MNs. Furthermore, the fact that Foxpl is expressed by dying MNs suggests that Hox proteins that are specific to the cervical segments may play a role in this type of cell death. In situ hybridizaiton for Hox genes revealed that Hoxc5, Hoxa3, Hoxa5 are expressed by cervical motoneurons and their rostro-caudal extents of expression cover the segments where early motoneuron death occurs. These Hox genes might be involved in the determination of motoneuron subgroups that under go cell death.

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  • Examination of the number of spinal motor neurons by using selective elimination of motor neurons

    Grant number：17590167

    2005 - 2006

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    SATO Noboru

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    Grant amount：\3500000 （ Direct Cost: \3500000 ）

    To clear how the number of spinal motor neurons is controlled during development (neurogenesis and elimination by cell death), selective elimination of motor neurons has been experimentally developed in this study. Bax, a pro-apoptotic member of the Bcl-2 family, was examined as executioner for motor neurons. To introduce Bax specifically into motor neurons during the period of early PCD, we have used in ovo electroporation coupled with the tet regulatory system. The reverse tetracycline-controlled transactivator was expressed under the control of the motor neuron specific HB9 promoter to target gene expression to spinal motor neurons. When gain-of-function Bax mutants were introduced into chick cervical motor neurons by this method, the number of dying motor neurons was significantly increased compared with those of control chick embryos. Naive Bax did not affect motor neuron survival by this method but significantly induced a large amount of cell death as soon as expressed in the spinal cord using the constitutive promoter such as the CMV promoter for their expression. Taken together, these strategies examined in this study will allow spatially and temporally controlled elimination of spinal motor neurons and will give specific insight into how the number of spinal motor neurons is regulated during development.

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  • Involvement of transcription factors in early motor neuron cell death in cervical segments of avian embryos

    Grant number：16500223

    2004 - 2005

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YAGINUMA Hiroyuki, SATO Noboru, HOMMA Syunsaku

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    Grant amount：\3700000 （ Direct Cost: \3700000 ）

    We previously reported that cell death of cervical motor neurons in early avian embryo occurs only in a subpopulation of motoneurons(MNs) that do not express Lim3, a member of LIM-HD transcription factors. In the present study, to elucidate mechanisms that determine cells to die, we clarified development of subtypes of MNs in the cervical and thoracic spinal cord. We examined correlations between birthdates of MNs and their final locations, detailed migration patterns, and change of expression patterns of LIM-HD transcription factors (Isl1, Isl2 and Lim3) and MNR2 protein in the chick embryo.
    Detailed analysis of expression patterns of Isl1, Isl2 and Lim3 and MNR2 revealed that these four marker proteins were once expressed by all motoneurons in both cervical and thoracic segments. However, Lim3 expression was lost in subpopulations of MNs by E4. In thoracic segments this Lim3-negative population became MNs in the lateral division of the medial motor column that innervate intercostal muscles, whereas in the cervical spinal cord this population disappeared by E5 because of cell death. Both populations became postmitotic in similar developmental stages and are located in similar regions of the motoneurons column. This consistency suggests that two populations are analogous neuronal groups. Difference of rostrocaudal differentiation of the spinal cord, which is determined by expression of Hox transcription factors, may determine different fates of the two populations.
    Although we pursued this possibility, we could not obtain decisive results within the period of this research project.

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  • Programmed cell death of developing neurons following Bax overexpression

    Grant number：15590165

    2003 - 2004

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    SATO Noboru

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    Grant amount：\3600000 （ Direct Cost: \3600000 ）

    Bax is a pro-apoptotic protein that is required for programmed cell death (PCD) of many neuronal populations. Here we show that, during an early period of retinal PCD and in naturally occurring sensory and motor neuron (MN) death in the spinal cord, Bar delivery results in enhanced death of these neural populations. In contrast, Bax overexpression fails to enhance an early phase of MN death that occurs in the cervical spinal cord, although overexpressed Bax appears to be activated in dying MNs. Bax overexpression does not also affect the survival of immature neurons prior to the PCD period. Taken together, these data provide the first in vivo evidence suggesting that Bax appears to act selectively as an executioner only in neurons undergoing PCD. Furthermore, although Bax appears to mediate the execution pathway for PCD, the effect of Bax overexpression on susceptibility to death differs between different neuronal populations.

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  • mechanisms of early motor neuron cell death in cervical segments of avian embryos

    Grant number：14580731

    2002 - 2003

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YAGINUMA Hiroyuki, SATO Noboru, HOMMA Shunsaku

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    Grant amount：\4100000 （ Direct Cost: \4100000 ）

    In the avian embryo spinal cord, motoneurons (MNs) undergo programmed cell death (PCD) at two distinct periods. One is observed at relatively later stages (E6-E10, in the chick) and involves all segments of the spinal cord. By contrast, the other occurs at relatively earlier stages (E4-E5) and only in the non-limb innervating cervical spinal cord. To determine the identity of the dying MNs in the early type of cell death, we examined expression of subgroup-specific MN markers (Isl1, Isl2, Lim3 and MNR2) in the dying MNs of the chick embryo. Quantitative analysis revealed that PCD occurs only in a subgroup of MNs that express Isl1, Isl2 and MNR2 but do not express Lim3. MNs of this subgroup become postmitotic between E3 (-) and E3.5 and appear as a distinct subgroup in the dorsolateral region of the ventral horn by E4 after losing Lim3 expression. However, they disappear by E5. Following introducing Bcl-2 gene with retroviral vector, cervical MNs were rescued from cell death. After the period of cell death (E5), we observed that, in the infected embryos, there was an additional subgroup of MNs that expressed Isl1 and Isl2 but did not express Lim3. Similar MNs appear also in the thoracic region and develop into MNs that innervate intercostal muscles. These results suggest that this type of PCD of MN in the cervical spinal cord occurs only in the Lim3-negative subgroup of MNs that correspond to MNs innervating intercostal muscles. To further examine the relations between Lim3 expression and cell death, we infected one side of the spinal cord with the retrovirus vector carrying chick Lim3 cDNA using electroporation technique. On the infected side, the number of dying MNs markedly decreased at E4.5 and the number of healthy MNs increased after the period of cell death (E5.5). These results suggest that the downregulation of Lim3 is involved in mechanisms that determine cells to die in the early type of cell death in the cervical spinal cord.

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  • 脊髄運動ニューロンの発生におけるBMPによる情報伝達の役割

    Grant number：13770013

    2001 - 2002

    System name：科学研究費助成事業

    Research category：若手研究(B)

    Awarding organization：日本学術振興会

    佐藤 昇

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    Grant amount：\2100000 （ Direct Cost: \2100000 ）

    本研究課題は、BMPの内在性インヒビターであるnogginやBMP受容体のdominant-negative変異体をレトロウイルスベクター(RCASBP)を用いてニワトリ胚で発現させることによって、BMPシグナル伝達をin vivoで阻害することによりその脊髄運動ニューロンの発生に及ぼす影響を検討するものである。まずRCASBPを用いた遺伝子導入法を確立する目的で、細胞死を抑制することで知られるBcl-2を運動ニューロン死の時期の時期に発現させてニューロン死が影響を受けるか検討した。その結果Bcl-2が発生早期に起きる頚髄運動ニューロン死を抑制することが明らかになった(Sato, et al. 2002)。このことからRCASBPレトロウイルスベクターがニワトリ胚の脊髄運動ニューロンへ遺伝子導入するための有力な手法であることが確認されたため、nogginを組み込んだウイルスを胚に感染させたところ、胚全体の発生が著しく損なわれそのままの実験系では脊髄運動ニューロンの発生に及ぼす影響を評価することが困難であった。これはnogginの持続的且つ広範囲な発現のためと考えられたため、導入遺伝子発現の時間的な制御を目的としてTet regulatory systemをこのレトロウイルスに組み込んで機能するかを検討した。その結果、ドキシサイクリン投与によって遺伝子発現が効率よく誘導されることが確認された(Sato, et al. 2002)。現在運動ニューロン特異的な発現を目指して各種の転写調節領域を検討している。当初目的には未だ至っていないが、目的達成のためのステップは確実にクリアしており今後さらに推進する予定である.

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  • 増殖型トリレトロウイルスベクターを用いた遺伝子導入法による神経細胞死機構の解析

    Grant number：11770006

    1999 - 2000

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    佐藤 昇

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    Grant amount：\2200000 （ Direct Cost: \2200000 ）

    本年度は前年度の研究成果を踏まえて、Bcl-2遺伝子を増殖型トリレトロウイルスベクター(RCASBP)を用いて鶏胚脊髄運動ニューロンへ導入して細胞死への影響を検討した。
    1)鶏胚(E4.5;stage24)の頚髄前角においてはpyknosisの形態像を伴った細胞死(アポトーシス)が多く認められるが、RCASBP(B)bcl-2を感染させた鶏胚では、頚髄の前角においてpyknosisの形態像が著明に減少していた。またアポトーシスに特徴的なDNAの断片化をTUNEL反応によって調べると、野生型やRCASBP(B)EGFPを感染させた鶏胚ではTUNEL陽性細胞が頚髄前角に多く認められたが、RCASBP(B)bcl-2を感染させた鶏胚においてはTUNEL陽性細胞は著明に減少していた。
    2)頚髄運動ニューロンの細胞死が始まる直前(E4;stage23)の運動ニューロン数を運動ニューロン特異的なマーカーであるislet-1/2に対する免疫染色によって検討したところ、野生型の胚、RCASBP(B)EGFPを感染させた胚、RCASBP(B)Bcl-2を感染させた胚の間でislet-1/2陽性細胞数に差は認められなかった。
    3)頚髄運動ニューロンの細胞死が終了した後(E5;stage26)の運動ニューロン数を同様に比較したところ、RCASBP(B)Bcl-2を感染させた胚では他に比べて明らかにislet-1/2陽性細胞が増加していた。
    4)以上から鶏胚(E4.5)における頚髄運動ニューロン死はBcl-2分子を導入することによって抑制されることが明らかになった。本研究によって頚髄運動ニューロン死に関与する分子の一つが初めて明らかにされ、また増殖型トリレトロウイルスベクターが鶏胚の発生研究において有用な手法であることが確認された。

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  • MECHANISNS OF NEURONAL DEQTH IN THE RAT (SHRSP) CEREBRAL CORTEX FOLLOEING FOCAL PERMANENT ISCHEMIA BY MIDDLE CEREBRAL ARTERY OCCLUSION

    Grant number：07680828

    1995 - 1997

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    NITATORI Tohru

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    Grant amount：\2200000 （ Direct Cost: \2200000 ）

    The cortical neurons are known to be vulnerable to anoxic, which in neuropathological changes of the neurons within the infarcted area. In the present study, we examined early histo-pathological changes in the cortical neurons after focal cerebrai, ischemia, induced by permanent unilateral occlusion of the middle cerebral artery (MCA). In the experimental animals infarcted cortical neurons within the focal wrea at the territory of MCA rapidly underwent cell death, while the neurins within ischemic penumbra exhibited relatively delayd neuronal death after ischemic insult. It remain, however, undefined whether death of these neurons are necrosis or apoptosis. We examined the degenerating process of the cortical neurons within the focal area and ischemic penumbra of cerebral cortex after focal ischemia. At 2 hrs after ischemic insults neurons within the focal area already changed their feature into relatively expanded shapes. Plasma membrane of these neurons was broken into pieces and fragments of disintegrated organelles scattered whithin cytoplasm. Expanded Nuclei of these broken into pieces and fragments of disintegrated oranelles scattered within cytoplasm. Expanded Nuclei of these neurons expressed TUNEL positive reaction. On the other hand, typical necrotic swelling neurons and highiy electron dense small ones were detected within the ischemic penumbra at 6 frs after ischemia. The latter neurons exhibited cell shrinkage accompanied with an increase in immunoreactivity for iysosmal cystein proteinases. Nuclei of these neurons showed TUNEL positive reacition from 1 to 3 days after insults. Degenerated neurons were heterophagocytosed by phagocytes invaded into the area. These results suggest that aduth death of the cortical neurons within the focal area after focal ischemia by MCA occlusion is necrotic, whereas neuronal death the ischemic penumbra consisted of necrotis and apoptoti.

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  • Apoptosis of CA1 pyramidal neurons in the hippocampus after brief forebrain ischemia and its prevention

    Grant number：07458201

    1995 - 1997

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    UCHIYAMA Yasuo, OHSAWA Yoshiyuki, GOTOW Takahiro, WATANABE Tsuyoshi

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    Grant amount：\7500000 （ Direct Cost: \7500000 ）

    1) PC12 cells undergo apoptosis when cultured under serum deprivation. In this situation, the activity of caspase-3-like proteinases was elevated, and the survival rate could be maintained by treatment with acetyl (AC)-DEVD-CHO,a specific inhibitor of caspase-3. In a culture of PC12 cells with AC-DEVD-CHO,where caspase-3-like proteinases are not activated, CA074, a specific inhibitor of cathepsin B induced apoptosis of the cells. This ability of CA074 was also replaced by cathepsin B antisense oligonucleotides. By double staining of TUNEL and activated caspase-3, the dying cells treated with CA074 were positive for TUNEL staining but negative for caspase-3. Ultrastructures of the cells were relatively large and had nuclei with chromatin condensation, suggesting that they died by apoptosis. Thus cell death effect by CA074 or the cathepsin B antisense were inhibited by the addition of pepstatin A,a lysosomal aspartic proteinase inhibitor, or cathepsin D antisense. The results suggest that a novel pathway of apoptosis exists, which is regulated by lysosomal cathepsins, and in which cathepsin D acts as a death factor, but that this death-inducing activity is usually suppressed by cathepsin B.
    2) PC12 cells transfected with the human bcl-2 gene can survive when cultured under serum deprivation. In this situation, the transfected cells extended neurite-like processes. Culture media of the transfected cells contained factor (s) which rescued wild-type PC12 cells following serum withdrawal. We therefore partially purified the factor and separated it by native SDSPAGE.From this, the N-terminal amino acid sequence of the factor was decided and the protein was found to be novel. Following the routine method of cDNA cloning, the cDNA clones of the factor protein were isolated, consisting of 2332 bp of total sequence having an ORF of 768 bp, encoding a protein of 256 amino acids. The predicted amino acid sequence has a signal sequence of 23 amino acid and an active form sequence of 233 amino acid. Antibodies against synthesized peptides corresponding to several parts of the protein indicated that the molecular weight of the protein is approximately 35 kD by SDSPAGE and Western blotting. Transfection study of the cloned cDNA into PC12 cells demonstrated that the cells can survive following serum withdrawal. We, therefore, named the factor as PCTF35.

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  • ラットIch-1/Nedd2遺伝子の構造及び発見の解析

    Grant number：07770015

    1995

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    佐藤 昇

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    Grant amount：\1000000 （ Direct Cost: \1000000 ）

    細胞死(アポトーシス)の細胞内機構を解析する目的で、細胞死の原因遺伝子の一つとして同定されNedd2/Ich1遺伝子のクローニングを試みた。マウスの塩基配列を参考に作製されたプライマーを用いてRT-PCR法を施行し増幅されたDNA断片をプローブとしてPC12細胞のcDNAライブラリーをスクリーニングした。得られたcDNAクローンの塩基配列を決定したところラットNedd2/Ich1は452アミノ酸残基から成ることが予想され、ヒト及びマウスのそれと高い相同性を有することが明かになった。ラットNedd2/Ich1のアミノ酸配列にはICE関連遺伝子ファミリーにみられるQACRGというシステインプロテアーゼとしての活性中心のモチーフも存在されていた。
    次にNedd2/Ich1遺伝子産物の機能を解析するために抗体作製を計画した。Nedd2/Ich1のC末端330-452アミノ酸残基部分をマルトース結合蛋白質のC末端に連結した融合蛋白質を大腸菌で作らせた。融合蛋白質をアミロースカラムで精製してウサギに免疫して抗Nedd2/Ich1血清を得た。この抗血清でPC12細胞のイムノブロットを施行したところNedd2/Ich1と予想されるバンドが分子量約28.000付近に確認された。PC12細胞は無血清培地で培養するとアポトーシスで死ぬが、その経時経過をNedd2/Ich1のイムノブロットで観察すると経過中Nedd2/Ich1のバンドが常に認められまたその発現量に著明な変化が認められないことから、1)Nedd2/Ich1の発現量ではなく活性の有無が重要である、2)Nedd2/Ich1の基質(未だに未知)の量が重要である、3)Nedd2/Ich1以外のICE関連遺伝子ファミリーが細胞死に関与している、などの可能性を今後検討する予定である。

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  • 原型癌遺伝子bcl-2の遺伝子発現による神経細胞死の回避とその生理的意義

    Grant number：07264236

    1995

    System name：科学研究費助成事業

    Research category：重点領域研究

    Awarding organization：日本学術振興会

    内山 安男, 似鳥 徹, 佐藤 昇, 和栗 聡

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    Grant amount：\2000000 （ Direct Cost: \2000000 ）

    これまでの研究から、Bcl-2蛋白は粗面小胞体や滑面小胞体、核膜、ミトコンドリアの外膜に局在することが報告されている。周知のごとく、アポトーシスは形態的な定義であり、核に初期変化があるとされてきた。特に、核クロマチンの凝縮、アポトーシス小体の形成時においてもミトコンドリアを初めとする細胞内小器官は形態的に正常である。しかし、近年の研究から、核DNAの断裂化が生じる時には、ミトコンドリアの機能も低下しているこが明らかにされている。さらに、Bcl-2はアポトーシスのみならず一部のネクローシス(呼吸鎖阻害により誘導された)をも回避することが分かった。これらの現象を理解するために、Bcl-2(およびBcl-X_L)の正確な局在をbcl-2/bcl-X_L遺伝子を導入したPC12細胞(PC-bcl/PC-bolx細胞)で免疫組織細胞化学的に検討した。免疫反応には、ヒト、マウスBcl-2/Bcl-x蛋白あるいはその合成ペプチドに対するポリクローナルあるいはモノクローナル抗体を用いた。共焦点レーザー顕微鏡でPC-bcl/bclx細胞を観察すると、Bcl-2/Bcl-x蛋白に対する細顆粒状の免疫陽性反応が細胞質や神経突起に見られた。凍結超薄切片-金コロイド法によって、Bcl-2/Bcl-x蛋白の局在をみると、Bcl-2/Bcl-x蛋白の抗原性を示す金コロイド粒子は主にミトコンドリアの内膜上に認められた。金粒子は小胞構造にも見られたが、核膜に沈着する金粒子は認められなかった。神経突起内に存在するミトコンドリアの内膜にも金粒子の局在が認められた。同蛋白陽性の金粒子は核にも見られたが、非特異的な局在との差は見られなかった。脊髄前角細胞、肝細胞においても同様の所見が得られた。現在のところ、Bcl-2およびその関連蛋白がミトコンドリア内膜のいかなる機構と関与するかは不明であるが、本研究結果は、アポトーシスを回避する機構にミトコンドリアが関与する可能性を示唆するものと思われる。

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  • 神経内分泌細胞におけるシステインプロテアーゼインヒビターの機能解析

    Grant number：06770018

    1994

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    佐藤 昇

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    Grant amount：\900000 （ Direct Cost: \900000 ）

    細胞質に存在するリソゾームシステインプロテアーゼの一つであるシスタチンβのPC12細胞における機能を明らかにする目的でアンチセンスオリゴヌクレオチド法によるシスタチンβの発現抑制を試みた。複数のアンチセンスオリゴヌクレオチドを用意したが有為な発現抑制は認められなかった。特にNGFで神経様に分化させる実験など長時間におよぶ系では安定した結果を得るのが難しいと考えられた。そこでアンチセンスオリゴヌクレオチド法による一過性の発現抑制ではなくアンチセンスベクターによる恒常的な発現抑制の系を検討することにした。
    その手始めとしてPC12細胞が発現ベクター導入によって持続的かつ安定な発現クローンを得るのに適した細胞であるか検討してみた。ヒト原型癌遺伝子bc1-2のcDNAをRSV-LTRプロモーターに連結したベクターを作製しリン酸カルシウム法によりPC12細胞に遺伝子を導入したところ6つの安定発現株を得た。いずれの株においてもヒトbc1-2がmRNA及び蛋白の両方のレベルでNGFによる神経分化誘導や血清除去によるアポトーシスの誘導刺激においても安定して発現していることをノーザンブロット法及びイムノブロット法にて確認した。このことよりRSV-LTRプロモーターによって発現が支配されるベクターがPC12細胞において有効に機能することが明らかになった。そこで現在シスタチンβのcDNAをRSV-LTRプロモータに逆向きに組み込んだ発現ベクターを作製している。このベクターは恒常的にシスタチンβのアンチセンスmRNAを発現することが予想され、その結果PC12細胞におけるシスタチンβの蛋白レベルでの発現が抑制されることが期待できる。

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  • 原型癌遺伝子bcl-2の遺伝子発現による神経細胞死の回避とその生理的意義

    Grant number：06272229

    1994

    System name：科学研究費助成事業

    Research category：重点領域研究

    Awarding organization：日本学術振興会

    内山 安男, 佐藤 昇, 和栗 聡, 似鳥 徹

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    Grant amount：\2200000 （ Direct Cost: \2200000 ）

    ラット褐色細胞腫由来のPC12細胞は血清を含む培地で培養すると増殖し、培地から血清を除くとポトーシスに陥ることが知られている。さらに、PC12細胞は血清非存在下で神経栄養因子(NGF)を添加した培地で培養すると、突起を伸展して神経細胞様に分化する。このような特徴を備えたPC12細胞に、細胞死を回避する原型癌遺伝子として知られるbcl-2遺伝子を過剰発現することによって、細胞死とその回避について検討した。発現ベクターに組み込んだヒトbcl-2遺伝子を燐酸カルシウム法により、PC12細胞に過剰発現させた。mRNAと蛋白レベルで検討し、bcl-2を発現した細胞株6種を得た。これらの株を用いて、血清存在下で培養すると野生株と同様に増殖した。無血清下で培養すると、野生株とベクターのみを組み込んだ細胞は24時間後には多くの細胞が死に、4日以内に全ての細胞が死んだ。しかし、bcl-2を組み込んだ細胞では4日後にみると、全ての株で80から100%の生存を示した。さらに、血清非存在下で2週間培養を続けた結果、bcl-2を発現した細胞は突起を伸展し、NGF存在下で培養した細胞と同様に神経細胞様に分化した。この細胞はニューロフィラメントM陽性であった。本実験結果から、bcl-2遺伝子を組み込んだ細胞は、血清存在下では野生株と同様に増殖するが、血清非存在下では野生株と異なり生存し、追には神経細胞様に分化することが明らかになった。今後、さらに、この系を用いて、分化因子の同定とbcl-2が細胞を如何に生存させるのかを検討する。

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  • ウイルスベクタ-による遺伝子導入

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    Grant type：Competitive

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  • Gene transfer by viral vectors

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    Grant type：Competitive

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  • Neuronal cell death

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    Grant type：Competitive

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  • 神経細胞死

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    Grant type：Competitive

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Teaching Experience

  • 人体の構造と機能I

    2025
    Institution name：新潟大学

  • 基礎臨床統合II

    2025
    Institution name：新潟大学

  • 人体の構造と機能II

    2025
    Institution name：新潟大学

  • 臨床実習入門(OSCE)

    2024
    Institution name：新潟大学

  • 早期医学体験実習(EME)

    2024
    Institution name：新潟大学

  • 医学入門

    2024
    Institution name：新潟大学

  • 臨床実習入門(CBT)

    2024
    Institution name：新潟大学

  • 医学序説 II

    2022
    Institution name：新潟大学

  • 医学論文を読む(ジャーナルクラブ)B

    2021
    -
    2023
    Institution name：新潟大学

  • 医学序説 I

    2021
    Institution name：新潟大学

  • はじめての医学

    2020
    Institution name：新潟大学

  • 医学序説 II

    2020
    Institution name：新潟大学

  • 臓器別講義・演習Ⅱ

    2017
    Institution name：新潟大学

  • 臓器別講義・演習Ⅲ

    2017
    Institution name：新潟大学

  • 医学論文を読む(ジャーナルクラブ)B

    2016
    -
    2023
    Institution name：新潟大学

  • 医学論文を読む(ジャーナルクラブ)A

    2016
    -
    2020
    Institution name：新潟大学

  • 臓器別講義・演習Ⅰ

    2016
    -
    2017
    Institution name：新潟大学

  • 人体の構造と機能Ⅰ(肉眼解剖学)

    2015
    Institution name：新潟大学

  • 人体の構造と機能Ⅰ(解剖総論)

    2015
    Institution name：新潟大学

  • 生命倫理

    2015
    -
    2017
    Institution name：新潟大学

  • 医事法制

    2015
    -
    2016
    Institution name：新潟大学

  • 臨床実習II(clinical clerkship)

    2014
    -
    2017
    Institution name：新潟大学

  • 臨床医学講義(集中)

    2014
    -
    2017
    Institution name：新潟大学

  • 医学論文を読む

    2014
    -
    2015
    Institution name：新潟大学

  • 医学研究実習

    2011
    -
    2013
    Institution name：新潟大学

  • 人体の構造

    2009
    -
    2023
    Institution name：新潟大学

  • 人体の構造と機能I(解剖総論)

    2008
    -
    2014
    Institution name：新潟大学

  • 人体解剖学実習

    2008
    -
    2014
    Institution name：新潟大学

  • 先端医科学研究概説

    2008
    -
    2013
    Institution name：新潟大学

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