2021/10/20 更新

写真a

ミヤシタ サトシ
宮下 聡
MIYASHITA Satoshi
所属
脳研究所 助教
職名
助教
外部リンク

学位

  • 博士(理学) ( 2018年4月 )

  • 修士(理学) ( 2015年3月 )

研究キーワード

  • single cell RNAseq

  • 小脳

  • 発生

研究分野

  • ライフサイエンス / ゲノム生物学

  • ライフサイエンス / 細胞生物学  / 神経発生

  • ライフサイエンス / 神経科学一般  / 神経発生

経歴(researchmap)

  • 新潟大学脳研究所   システム脳病態学分野   助教

    2021年4月 - 現在

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  • 国立研究開発法人国立精神・神経医療研究センター   病態生化学研究部   流動研究員

    2018年4月 - 2021年3月

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  • 独立行政法人日本学術振興会

    2015年4月 - 2018年3月

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  • 国立研究開発法人国立精神・神経医療研究センター   病態生化学研究部(指導教官 星野幹雄)   研究生

    2011年10月 - 2018年3月

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経歴

  • 新潟大学   脳研究所   助教

    2021年4月 - 現在

学歴

  • 早稲田大学   先進理工学研究科   電気情報生命専攻 博士課程

    2015年4月 - 2018年3月

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  • 早稲田大学   先進理工学研究科   電気情報生命専攻修士課程

    2013年4月 - 2015年3月

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  • 早稲田大学   先進理工学部   電気情報生命工学科

    2009年4月 - 2013年3月

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所属学協会

 

論文

  • Cyclin D1 controls development of cerebellar granule cell progenitors through phosphorylation and stabilization of ATOH1. 国際誌

    Satoshi Miyashita, Tomoo Owa, Yusuke Seto, Mariko Yamashita, Shogo Aida, Masaki Sone, Kentaro Ichijo, Tomoki Nishioka, Kozo Kaibuchi, Yoshiya Kawaguchi, Shinichiro Taya, Mikio Hoshino

    The EMBO journal   e105712   2021年5月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cold Spring Harbor Laboratory  

    During development, neural progenitors are in proliferative and immature states; however, the molecular machinery that cooperatively controls both states remains elusive. Here, we report that cyclin D1 (CCND1) directly regulates both proliferative and immature states of cerebellar granule cell progenitors (GCPs). CCND1 not only accelerates cell cycle but also upregulates ATOH1 protein, an essential transcription factor that maintains GCPs in an immature state. In cooperation with CDK4, CCND1 directly phosphorylates S309 of ATOH1, which inhibits additional phosphorylation at S328 and consequently prevents S328 phosphorylation-dependent ATOH1 degradation. Additionally, PROX1 downregulates Ccnd1 expression by histone deacetylation of Ccnd1 promoter in GCPs, leading to cell cycle exit and differentiation. Moreover, WNT signaling upregulates PROX1 expression in GCPs. These findings suggest that WNT-PROX1-CCND1-ATOH1 signaling cascade cooperatively controls proliferative and immature states of GCPs. We revealed that the expression and phosphorylation levels of these molecules dynamically change during cerebellar development, which are suggested to determine appropriate differentiation rates from GCPs to GCs at distinct developmental stages. This study contributes to understanding the regulatory mechanism of GCPs as well as neural progenitors.

    DOI: 10.15252/embj.2020105712

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  • Pharmacological activation of SERCA ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice. 査読 国際誌

    Ken'ichiro Nogami, Yusuke Maruyama, Fusako Sakai-Takemura, Norio Motohashi, Ahmed Elhussieny, Michihiro Imamura, Satoshi Miyashita, Megumu Ogawa, Satoru Noguchi, Yuki Tamura, Jun-Ichi Kira, Yoshitsugu Aoki, Shin'ichi Takeda, Yuko Miyagoe-Suzuki

    Human molecular genetics   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscular weakness due to the loss of dystrophin. Extracellular Ca2+ flows into the cytoplasm through membrane tears in dystrophin-deficient myofibers, which leads to muscle contracture and necrosis. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) takes up cytosolic Ca2+ into the sarcoplasmic reticulum (SR), but its activity is decreased in dystrophic muscle. Here, we show that an allosteric SERCA activator, CDN1163, ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice. Administration of CDN1163 prevented exercise-induced muscular damage and restored mitochondrial function. In addition, treatment with CDN1163 for seven weeks enhanced muscular strength and reduced muscular degeneration and fibrosis in mdx mice. Our findings provide preclinical proof-of-concept evidence that pharmacological activation of SERCA could be a promising therapeutic strategy for DMD. Moreover, CDN1163 improved muscular strength surprisingly in wild-type mice, which may pave the new way for the treatment of muscular dysfunction.

    DOI: 10.1093/hmg/ddab100

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  • Notch Signaling between Cerebellar Granule Cell Progenitors. 査読 国際誌

    Toma Adachi, Satoshi Miyashita, Mariko Yamashita, Mana Shimoda, Konstantin Okonechnikov, Lukas Chavez, Marcel Kool, Stefan M Pfister, Takafumi Inoue, Daisuke Kawauchi, Mikio Hoshino

    eNeuro   2021年3月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cerebellar granule cells (GCs) are cells which comprise over 50% of the neurons in the entire nervous system. GCs enable the cerebellum to properly regulate motor coordination, learning, and consolidation, in addition to cognition, emotion and language. During GC development, maternal GC progenitors (GCPs) divide to produce not only postmitotic GCs but also sister GCPs. However, the molecular machinery for regulating the proportional production of distinct sister cell types from seemingly uniform GCPs is not yet fully understood. Here we report that Notch signaling creates a distinction between GCPs and leads to their proportional differentiation in mice. Among Notch-related molecules, Notch1, Notch2, Jag1, and Hes1 are prominently expressed in GCPs. In vivo monitoring of Hes1-promoter activities showed the presence of two types of GCPs, Notch-signaling ON and OFF, in the external granule layer (EGL). Single-cell RNA sequencing (scRNA-seq) and in silico analyses indicate that ON-GCPs have more proliferative and immature properties, while OFF-GCPs have opposite characteristics. Overexpression as well as knock-down (KD) experiments using in vivo electroporation showed that NOTCH2 and HES1 are involved cell-autonomously to suppress GCP differentiation by inhibiting NEUROD1 expression. In contrast, JAG1-expressing cells non-autonomously upregulated Notch signaling activities via NOTCH2-HES1 in surrounding GCPs, eventually suppressing their differentiation. These findings suggest that Notch signaling results in the proportional generation of two types of cells, immature and differentiating GCPs, which contributes to the well-organized differentiation of GCs.Significance StatementThis study is the first to succeed in visualization of Notch signaling in vivo during cerebellar development. Granule cell progenitors (GCPs) in the outermost layer of the developing cerebellum are a seemingly homogenous cell population, but this study revealed two types of GCPs; more proliferative Notch-ON-GCPs and more differentiative Notch-OFF-GCPs, the latter of which gradually give rise to postmitotic GCs. Our experiments suggest that NOTCH2 and HES1 are involved cell-autonomously to suppress GCP differentiation by inhibiting NEUROD1 expression. In contrast, JAG1-expressing cells non-autonomously upregulated Notch signaling activities via NOTCH2-HES1 in surrounding GCPs, suppressing their differentiation. This study gives new insights into the mechanisms controlling the differences within homogenous cell populations that direct proper and coordinated cell differentiation.

    DOI: 10.1523/ENEURO.0468-20.2021

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  • The role of SCFSkp2 and SCFβ-TrCP1/2 in the cerebellar granule cell precursors. 査読 国際誌

    Mariko Yamashita, Tomoo Owa, Ryo Shiraishi, Toma Adachi, Kentaro Ichijo, Shinichiro Taya, Satoshi Miyashita, Mikio Hoshino

    Genes to cells : devoted to molecular & cellular mechanisms   25 ( 12 )   796 - 810   2020年12月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A proper balance between proliferation and differentiation of cerebellar granule cell precursors (GCPs) is required for appropriate cerebellar morphogenesis. The Skp1-Cullin1-F-box (SCF) complex, an E3 ubiquitin ligase complex, is involved in polyubiquitination and subsequent degradation of various cell cycle regulators and transcription factors. However, it remains unknown how the SCF complex affects proliferation and differentiation of GCPs. In this study, we found that the scaffold protein Cullin1, and F-box proteins Skp2, β-TrCP1 and β-TrCP2 are expressed in the external granule layer (EGL). Knockdown of these molecules in the EGL showed that Cullin1, Skp2 and β-TrCP2 enhanced differentiation of GCPs. We also observed accumulation of cyclin-dependent kinase inhibitor p27 in GCPs when treated with a Cullin1 inhibitor or proteasome inhibitor. Furthermore, knockdown of p27 rescued enhancement of differentiation by Cullin1 knockdown. These results suggest that the SCF complex is involved in the maintenance of the proliferative state of GCPs through p27 degradation. In addition, inhibition of Cullin1 activity also prevented cell proliferation and enhanced accumulation of p27 in Daoy cells, a cell line derived from the sonic hedgehog subtype of medulloblastoma. This suggested that excess degradation of p27 through the SCF complex causes overproliferation of medulloblastoma cells.

    DOI: 10.1111/gtc.12813

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  • DSCAM regulates delamination of neurons in the developing midbrain. 査読 国際誌

    Nariko Arimura, Mako Okada, Shinichiro Taya, Ken-Ichi Dewa, Akiko Tsuzuki, Hirotomo Uetake, Satoshi Miyashita, Koichi Hashizume, Kazumi Shimaoka, Saki Egusa, Tomoki Nishioka, Yuchio Yanagawa, Kazuhiro Yamakawa, Yukiko U Inoue, Takayoshi Inoue, Kozo Kaibuchi, Mikio Hoshino

    Science advances   6 ( 36 )   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    For normal neurogenesis and circuit formation, delamination of differentiating neurons from the proliferative zone must be precisely controlled; however, the regulatory mechanisms underlying cell attachment are poorly understood. Here, we show that Down syndrome cell adhesion molecule (DSCAM) controls neuronal delamination by local suppression of the RapGEF2-Rap1-N-cadherin cascade at the apical endfeet in the dorsal midbrain. Dscam transcripts were expressed in differentiating neurons, and DSCAM protein accumulated at the distal part of the apical endfeet. Cre-loxP-based neuronal labeling revealed that Dscam knockdown impaired endfeet detachment from ventricles. DSCAM associated with RapGEF2 to inactivate Rap1, whose activity is required for membrane localization of N-cadherin. Correspondingly, Dscam knockdown increased N-cadherin localization and ventricular attachment area at the endfeet. Furthermore, excessive endfeet attachment by Dscam knockdown was restored by co-knockdown of RapGEF2 or N-cadherin Our findings shed light on the molecular mechanism that regulates a critical step in early neuronal development.

    DOI: 10.1126/sciadv.aba1693

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  • AUTS2 Regulation of Synapses for Proper Synaptic Inputs and Social Communication. 査読 国際誌

    Kei Hori, Kunihiko Yamashiro, Taku Nagai, Wei Shan, Saki F Egusa, Kazumi Shimaoka, Hiroshi Kuniishi, Masayuki Sekiguchi, Yasuhiro Go, Shoji Tatsumoto, Mitsuyo Yamada, Reika Shiraishi, Kouta Kanno, Satoshi Miyashita, Asami Sakamoto, Manabu Abe, Kenji Sakimura, Masaki Sone, Kazuhiro Sohya, Hiroshi Kunugi, Keiji Wada, Mitsuhiko Yamada, Kiyofumi Yamada, Mikio Hoshino

    iScience   23 ( 6 )   101183 - 101183   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    Impairments in synapse development are thought to cause numerous psychiatric disorders. Autism susceptibility candidate 2 (AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals with AUTS2 mutations.

    DOI: 10.1016/j.isci.2020.101183

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  • Expression of transcription factors and signaling molecules in the cerebellar granule cell development. 査読

    Shiraishi RD, Miyashita S, Yamashita M, Adachi T, Shimoda MM, Owa T, Hoshino M

    Gene expression patterns : GEP   34   119068   2019年8月

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    担当区分:筆頭著者  

    DOI: 10.1016/j.gep.2019.119068

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  • Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain 査読

    Tomoyuki Fujiyama, Satoshi Miyashita, Yousuke Tsuneoka, Kazumasa Kanemaru, Miyo Kakizaki, Satomi Kanno, Yukiko Ishikawa, Mariko Yamashita, Tomoo Owa, Mai Nagaoka, Yoshiya Kawaguchi, Yuchio Yanagawa, Mark A. Magnuson, Masafumi Muratani, Akira Shibuya, Yo-ichi Nabeshima, Masashi Yanagisawa, Hiromasa Funato, Mikio Hoshino

    Cell Reports   24 ( 1 )   79 - 94   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier B.V.  

    The mammalian brain undergoes sexual differentiation by gonadal hormones during the perinatal critical period. However, the machinery at earlier stages has not been well studied. We found that Ptf1a is expressed in certain neuroepithelial cells and immature neurons around the third ventricle that give rise to various neurons in several hypothalamic nuclei. We show that conditional Ptf1a-deficient mice (Ptf1a cKO) exhibit abnormalities in sex-biased behaviors and reproductive organs in both sexes. Gonadal hormone administration to gonadectomized animals revealed that the abnormal behavior is caused by disorganized sexual development of the knockout brain. Accordingly, expression of sex-biased genes was severely altered in the cKO hypothalamus. In particular, Kiss1, important for sexual differentiation of the brain, was drastically reduced in the cKO hypothalamus, which may contribute to the observed phenotypes in the Ptf1a cKO. These findings suggest that forebrain Ptf1a is one of the earliest regulators for sexual differentiation of the brain. Fujiyama et al. find that forebrain-specific Ptf1a-deficient mice (Ptf1a cKO) exhibit abnormalities in sexually dimorphic behaviors, reproductive organs, and severely altered expression of sex-biased genes, including Kiss1, in the hypothalamus in both sexes, which suggests that forebrain Ptf1a is one of the earliest regulators for sexual differentiation of the brain.

    DOI: 10.1016/j.celrep.2018.06.010

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  • Meis1 coordinates cerebellar granule cell development by regulating pax6 transcription, BMP signaling and atoh1 degradation 査読

    Tomoo Owa, Shinichiro Taya, Satoshi Miyashita, Mariko Yamashita, Toma Adachi, Koyo Yamada, Miwa Yokoyama, Shogo Aida, Tomoki Nishioka, Yukiko U. Inoue, Ryo Goitsuka, Takuro Nakamura, Takayoshi Inoue, Kozo Kaibuchi, Mikio Hoshino

    Journal of Neuroscience   38 ( 5 )   1277 - 1294   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Society for Neuroscience  

    Cerebellar granule cell precursors (GCPs) and granule cells (GCs) represent good models to study neuronal development. Here, we report that the transcription factor myeloid ectopic viral integration site 1 homolog (Meis1) plays pivotal roles in the regulation of mouse GC development. We found that Meis1 is expressed in GC lineage cells and astrocytes in the cerebellum during development. Targeted disruption of the Meis1 gene specifically in theGClineage resulted in smaller cerebella with disorganized lobules. Knock-down/knock-out (KO) experiments for Meis1 and in vitro assays showed that Meis1 binds to an upstream sequence of Pax6 to enhance its transcription in GCPs/GCs and also suggested that the Meis1–Pax6 cascade regulates morphology of GCPs/GCs during development. In the conditional KO (cKO) cerebella, many Atoh1-positive GCPs were observed ectopically in the inner external granule layer (EGL) and a similar phenomenon was observed in cultured cerebellar slices treated with a bone morphogenic protein (BMP) inhibitor. Furthermore, expression of Smad proteins and Smad phosphorylation were severely reduced in the cKO cerebella and Meis1-knock-down GCPs cerebella. Reduction of phosphorylated Smad was also observed in cerebellar slices electroporated with a Pax6 knock-down vector. Because it is known that BMP signaling induces Atoh1 degradation in GCPs, these findings suggest that the Meis1–Pax6 pathway increases the expression of Smad proteins to upregulate BMP signaling, leading to degradation of Atoh1 in the inner EGL, which contributes to differentiation from GCPs to GCs. Therefore, this work reveals crucial functions of Meis1 in GC development and gives insights into the general understanding of the molecular machinery underlying neural differentiation from neural progenitors.

    DOI: 10.1523/JNEUROSCI.1545-17.2017

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  • Dynamics of the cell division orientation of granule cell precursors during cerebellar development 査読

    Satoshi Miyashita, Toma Adachi, Mariko Yamashita, Takayuki Sota, Mikio Hoshino

    MECHANISMS OF DEVELOPMENT   147   1 - 7   2017年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The cerebellar granule cell (GC) system provides a good model for studying neuronal development. In the external granule layer (EGL), granule cell precursors (GCPs) rapidly and continuously divide to produce numerous GCs as well as GCPs. In some brain regions, the orientation of cell division affects daughter cell fate, thus the direction of GCP division is related to whether it produces a GCP or a GC. Therefore, we tried to characterize the orientation of GCP division from embryonic to postnatal stages and to identify an environmental cue that regulates the orientation. By visualizing chromatin in EGL GCPs at M-phase, we found that the directions of cell divisions were not random but dynamically regulated during development. While horizontal and vertical divisions were equivalently observed in embryos, horizontal division was more frequently observed at early postnatal stages. Vertical division became dominant at late cerebellar developmental stages. Administration of a SHH inhibitor to cultured cerebellar slices resulted in randomized orientation of cell division, suggesting that SHH signaling regulates the direction of cell division. These results provide fundamental data towards understanding the development of GCs. (C) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.mod.2017.06.002

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  • Origins of oligodendrocytes in the cerebellum, whose development is controlled by the transcription factor, Sox9 査読

    Ryoya Hashimoto, Kei Hori, Tomoo Owa, Satoshi Miyashita, Kenichi Dewa, Norihisa Masuyama, Kazuhisa Sakai, Yoneko Hayase, Yusuke Seto, Yukiko U. Inoue, Takayoshi Inoue, Noritaka Ichinohe, Yoshiya Kawaguchi, Haruhiko Akiyama, Schuichi Koizumi, Mikio Hoshino

    MECHANISMS OF DEVELOPMENT   140   25 - 40   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification of oligodendrocyte progenitor cells (OPCs) begins early in development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. However, for oligodendrocytes in the cerebellum, the developmental origins and the molecular machinery to control these distinct steps remain unclear. By in vivo fate mapping and immunohistochemical analyses, we obtained evidence that the majority of oligodendrocytes in the cerebellum originate from the Olig2-expressing neuroepithelial domain in the ventral rhombomere 1 (r1), while about 6% of cerebellar oligodendrocytes are produced in the cerebellar ventricular zone. Furthermore, to elucidate the molecular determinants that regulate their development, we analyzed mice in which the transcription factor Sox9 was specifically ablated from the cerebellum, ventral r1 and caudal midbrain by means of the Cre/loxP recombination system. This resulted in a delay in the birth of OPCs and subsequent developmental aberrations in these cells in the Sox9-deficient mice. In addition, we observed altered proliferation of OPCs, resulting in a decrease in oligodendrocyte numbers that accompanied an attenuation of the differentiation and an increased rate of apoptosis. Results from in vitro assays using oligodendrocyte-enriched cultures further supported our observations from in vivo experiments. These data suggest that Sox9 participates in the development of oligodendrocytes in the cerebellum, by regulating the timing of their generation, proliferation, differentiation and survival. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.mod.2016.02.004

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  • Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum 査読

    Yusuke Seto, Tomoya Nakatani, Norihisa Masuyama, Shinichiro Taya, Minoru Kumai, Yasuko Minaki, Akiko Hamaguchi, Yukiko U. Inoue, Takayoshi Inoue, Satoshi Miyashita, Tomoyuki Fujiyama, Mayumi Yamada, Heather Chapman, Kenneth Campbell, Mark A. Magnuson, Christopher V. Wright, Yoshiya Kawaguchi, Kazuhiro Ikenaka, Hirohide Takebayashi, Shin'ichi Ishiwata, Yuichi Ono, Mikio Hoshino

    NATURE COMMUNICATIONS   5   3337   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    In the cerebellum, all GABAergic neurons are generated from the Ptf1a-expressing ventricular zone (Ptf1a domain). However, the machinery to produce different types of GABAergic neurons remains elusive. Here we show temporal regulation of distinct GABAergic neuron progenitors in the cerebellum. Within the Ptf1a domain at early stages, we find two subpopulations; dorsally and ventrally located progenitors that express Olig2 and Gsx1, respectively. Lineage tracing reveals the former are exclusively Purkinje cell progenitors (PCPs) and the latter Pax2-positive interneuron progenitors (PIPs). As development proceeds, PCPs gradually become PIPs starting from ventral to dorsal. In gain-and loss-of-function mutants for Gsx1 and Olig1/2, we observe abnormal transitioning from PCPs to PIPs at inappropriate developmental stages. Our findings suggest that the temporal identity transition of cerebellar GABAergic neuron progenitors from PCPs to PIPs is negatively regulated by Olig2 and positively by Gsx1, and contributes to understanding temporal control of neuronal progenitor identities.

    DOI: 10.1038/ncomms4337

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書籍等出版物

  • Handbook of the Cerebellum and Cerebellar Disorders 2021

    ( 担当: 共著)

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講演・口頭発表等

  • Mitosis-dependent histone deacetylation controls the timing of differentiation in cerebellar granule cell precursors. 国際会議

    宮下 聡

    the 3rd Korean-Japanese Developmental Biology Meeting.  2018年6月 

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  • Mitosis-dependent histone deacetylation regulates the mitotic window of cerebellar granule cell precursors.

    宮下 聡

    第11回 神経発生討論会  2018年3月 

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  • Prox1 regulates the cell cycle exit of cerebellar granule cell precursors through suppression of a cell cycle-related gene.

    宮下 聡

    第39回日本神経科学大会  2016年7月 

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  • 小脳顆粒細胞におけるProx1の機能解析

    宮下 聡

    第9回神経発生討論会  2016年3月 

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  • Prox1 switches granule cell precursors from proliferative to differentiative states in cerebellum.

    宮下 聡

    第7回 神経発生討論会  2014年3月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Prox1 regulates the last mitosis of cerebellar granule cell precursors.

    宮下 聡

    平成25年度 包括脳ネットワーック 夏のワークショップ  2013年8月 

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    記述言語:日本語   会議種別:ポスター発表  

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受賞

  • 若手シンポ優秀賞

    2021年2月   CBIR若手インスパイアシンポジウム  

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  • 若手優秀発表賞

    2019年12月   次世代脳冬のシンポジウム2019  

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  • 最優秀口頭発表賞

    2018年3月   第11回神経発生討論会  

    宮下 聡

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  • Developmental Neuroscience Award

    2016年3月   第9回神経発生討論会  

    宮下 聡

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  • Developmental Neuroscience Award

    2014年3月   第7回神経発生討論会  

    宮下 聡

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  • 若手優秀発表賞

    2013年8月   包括型脳科学研究推進支援ネットワーク  

    宮下 聡

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共同研究・競争的資金等の研究

  • Unipolar brush cellsが小脳機能に果たす役割の解明

    研究課題/領域番号:20K15919  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    宮下 聡

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • G1期のダイナミックな変化を介した神経前駆細胞の細胞周期停止メカニズム

    研究課題/領域番号:15J06259  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    宮下 聡

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    配分額:2500000円 ( 直接経費:2500000円 )

    年次計画において、3年目では、G1期の長さに応じて発現が変動する遺伝子を同定したのち、①その遺伝子の機能を解析すること、②研究成果をまとめ、論文として投稿する計画であった。
    ①これまでに、ホメオボックス型転写因子であるProx1が細胞周期関連分子CyclinD1プロモーター領域に結合し、ヒストンの脱アセチル化をすることによってbHLH型転写因子であるAtoh1の発現制御に関与していることを見出していた。本年度は、CyclinD1によるAtoh1の発現制御機構の解明を目的に解析を行った。in vitroにおけるAtoh1タンパクの発現に着目したところ、 CyclinD1の存在がAtoh1タンパクの安定化に寄与していることを見出した。さらに、その制御がサイクリン依存性キナーゼであるCdkを介したものである可能性を示唆するデータを得た。以上の成果は、神経細胞ではこれまであまり報告がなかったCdkとCyclinD1によるタンパク安定化機構に関する新たな知見を提供するだけでなく、CdkとCyclinD1というG1期の長さを直接制御する重要な分子が、本来の機能である細胞周期の制御と同時に、細胞の未分化性を制御するタンパクの発現を制御するという非常に興味深い結果である。つまり、G1期の長さのダイナミックな変化は、それと並行して起こるCyclinD1-Cdkによる未分化維持に関わる分子のタンパク制御のひとつの指標であると考えられる。
    ②採用期間中に行った神経前駆細胞の運命を決定する分裂のメカニズムに関する研究をまとめた論文をMechanisms of Development誌に投稿した。さらに、上述の①とこれまで行ってきた研究をまとめた論文の投稿を準備中である。

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  • 小脳神経細胞の個性獲得および分化の制御機構

    研究課題/領域番号:15H04268  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    星野 幹雄, 大輪 智雄, 宮下 聡

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    配分額:18070000円 ( 直接経費:13900000円 、 間接経費:4170000円 )

    我々はいくつかの癌を引き起こすことが知られているMeis1遺伝子が発達途上の小脳顆粒細胞とその前駆細胞で発現することを見出した。この遺伝子を破壊したノックアウトマウスでは、小脳が小さくなり、その内部構造が乱れてしまう。さらにMEIS1タンパク質がPax6遺伝子の発現を誘導すること、誘導されたPAX6がBMPシグナルを促進すること、そしてBMPシグナルがATOH1の分解を引き起こし、その結果として前駆細胞から顆粒細胞への分化を促進することが明らかになった。

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