記述言語：日本語   出版者・発行元：新潟歯学会  

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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  

Cleft palate is one of the most common congenital diseases. Therefore, elucidating the molecular mechanisms of palate development is crucial for basic science and the clinical field. Cleft palate in mouse with targeted gene mutation is an excellent experimental model for clarifying the mechanisms driving palate development. Cleft palate occurs in two forms: a cleft between the primary and secondary palates (primary cleft palate) and a cleft between the secondary palates (secondary cleft palate). It remains unclear whether primary palate development is under similar molecular control as secondary palate formation, since most of studies have focused on secondary palate development using mutant mice. CL/Fraser (CL/Fr) is a mouse strain that often exhibits spontaneous primary cleft palate; however, the molecular changes in primary cleft palate in CL/Fr mice are not fully understood. Several signaling pathways, including Shh, Fgf, Bmp, and Wnt signaling, have been shown to play key roles in secondary palate development. In the present study, we found that Shh and Wnt signaling pathways were downregulated in the primary cleft palate region in CL/Fr mice.

DOI： 10.1016/j.ajoms.2019.12.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder characterized by abnormal structures and functions of the ectoderm-derived organs, including teeth. HED patients exhibit a variety of dental symptoms, such as hypodontia. Although disruption of the EDA/EDAR/EDARADD/NF-κB pathway is known to be responsible for HED, it remains unclear whether this pathway is involved in the process of enamel formation. EXPERIMENTAL SUBJECTS AND METHODS: To address this question, we examined the mice overexpressing Ikkβ (an essential component required for the activation of NF-κB pathway) under the keratin 5 promoter (K5-Ikkβ). RESULTS: Upregulation of the NF-κB pathway was confirmed in the ameloblasts of K5-Ikkβ mice. Premature abrasion was observed in the molars of K5-Ikkβ mice, which was accompanied by less mineralized enamel. However, no significant changes were observed in the enamel thickness and the pattern of enamel rods in K5-Ikkβ mice. Klk4 expression was significantly upregulated in the ameloblasts of K5-Ikkβ mice at the maturation stage, and the expression of its substrate, amelogenin, was remarkably reduced. This suggests that abnormal enamel observed in K5-Ikkβ mice was likely due to the compromised degradation of enamel protein at the maturation stage. CONCLUSION: Therefore, we could conclude that the overactivation of the NF-κB pathway impairs the process of amelogenesis.

DOI： 10.1111/odi.13384

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Periodic patterning of iterative structures is diverse across the animal kingdom. Clarifying the molecular mechanisms involved in the formation of these structures helps to elucidate the genetic commonality of developmental processes, as organs with these structures are believed to share the same molecular mechanisms and fundamental processes. Palatal rugae are periodic corrugated structures on the hard palate and are conserved in all mammals. Although the numbers and patterns of the palatal rugae are species specific, they are consistent in each mammalian species, except humans. HIGHLIGHT: Palatal rugae development is thus under strict genetic control in most mammals and is an excellent model to investigate the genetic commonality of developmental processes to form periodic patterning. CONCLUSION: This review highlights the current understanding of the molecular mechanisms of palatal rugae development.

DOI： 10.1016/j.job.2019.12.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mandible is a crucial organ in both clinical and biological fields due to the high frequency of congenital anomalies and the significant morphological changes during evolution. Primary cilia play a critical role in many biological processes, including the determination of left/right axis patterning, the regulation of signaling pathways, and the formation of bone and cartilage. Perturbations in the function of primary cilia are known to cause a wide spectrum of human diseases: the ciliopathies. Craniofacial dysmorphologies, including mandibular deformity, are often seen in patients with ciliopathies. Mandibular development is characterized by chondrogenesis and osteogenesis; however, the role of primary cilia in mandibular development is not fully understood. To address this question, we generated mice with mesenchymal deletions of the ciliary protein, Ift88 (Ift88fl/fl ;Wnt1Cre). Ift88fl/fl ;Wnt1Cre mice showed ectopic mandibular bone formation, whereas Ift88 mutant mandible was slightly shortened. Meckel's cartilage was modestly expanded in Ift88fl/fl ;Wnt1Cre mice. The downregulation of Hh signaling was found in most of the mesenchyme of Ift88 mutant mandible. However, mice with a mesenchymal deletion of an essential molecule for Hh signaling activity, Smo (Smofl/fl ;Wnt1Cre), showed only ectopic mandibular formation, whereas Smo mutant mandible was significantly shortened. Ift88 is thus involved in chondrogenesis and osteogenesis during mandibular development, partially through regulating Sonic hedgehog (Shh) signaling.

DOI： 10.1111/joa.13096

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Periodic patterning of iterative structures is a fundamental process during embryonic development, since these structures are diverse across the animal kingdom. Therefore, elucidating the molecular mechanisms in the formation of these structures promotes understanding of the process of organogenesis. Periodically patterned ridges, palatal rugae (situated on the hard palate of mammals), are an excellent experimental model to clarify the molecular mechanisms involved in the formation of periodic patterning of iterative structures. Primary cilia are involved in many biological events, including the regulation of signaling pathways such as Shh and non-canonical Wnt signaling. However, the role of primary cilia in the development of palatal rugae remains unclear. We found that primary cilia were localized to the oral cavity side of the interplacode epithelium of the palatal rugae, whereas restricted localization of primary cilia could not be detected in other regions. Next, we generated mice with a placodal conditional deletion of the primary cilia protein Ift88, using ShhCre mice (Ift88 fl/fl;ShhCre). Highly disorganized palatal rugae were observed in Ift88 fl/fl;ShhCre mice. Furthermore, by comparative in situ hybridization analysis, many Shh and non-canonical Wnt signaling-related molecules showed spatiotemporal expression patterns during palatal rugae development, including restricted expression in the epithelium (placodes and interplacodes) and mesenchyme. Some of these expression were found to be altered in Ift88 fl/fl;ShhCre mice. Primary cilia is thus involved in development of palatal rugae.

DOI： 10.1016/j.gep.2019.119062

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tooth cusp is a crucial structure, since the shape of the molar tooth is determined by number, shape, and size of the cusp. Bone morphogenetic protein (Bmp) signaling is known to play a critical role in tooth development, including in initiation. However, it remains unclear whether Bmp signaling is also involved in cusp formation. To address this question, we examined cusp in two different transgenic mouse lines: mice with overexpression of Bmp4 (K14-Bmp4), and those with Bmp inhibitor, Noggin, (K14-Noggin) under keratin14 (K14) promoter. K14-Noggin mice demonstrated extra cusps, whereas reduced number of cusps was observed in K14-Bmp4 mice. To further understand how Bmps are expressed during cusp formation, we performed whole-mount in situ hybridisation analysis of three major Bmps (Bmp2, Bmp4, and Bmp7) in murine maxillary and mandibular molars from E14.5 to P3. The linear expressions of Bmp2 and Bmp4 were observed in both maxillary and mandibular molars at E14.5. The expression patterns of Bmp2 and Bmp4 became significantly different between the maxillary and mandibular molars at E16.5. At P3, all Bmps were expressed in all the cusp regions of the maxillary molar; however, the patterns differed. All Bmps thus exhibited dynamic temporo-spatial expression during the cusp formation. It could therefore be inferred that Bmp signaling is involved in regulating cusp formation.

DOI： 10.1016/j.gep.2019.04.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The development of the maxillary bone is under strict molecular control because of its complicated structure. Primary cilia play a critical role in craniofacial development, since defects in primary cilia are known to cause congenital craniofacial dysmorphologies as a wide spectrum of human diseases: the ciliopathies. The primary cilia also are known to regulate bone formation. However, the role of the primary cilia in maxillary bone development is not fully understood. DESIGN: To address this question, we generated mice with a mesenchymal conditional deletion ofIft88 using the Wnt1Cre mice (Ift88fl/fl;Wnt1Cre). The gene Ift88 encodes a protein that is required for the function and formation of primary cilia. RESULTS: It has been shown thatIft88fl/fl;Wnt1Cre mice exhibit cleft palate. Here, we additionally observed excess bone formation in the Ift88 mutant maxillary process. We also found ectopic apoptosis in the Ift88 mutant maxillary process at an early stage of development. To investigate whether the ectopic apoptosis is related to the Ift88 mouse maxillary phenotypes, we generated Ift88fl/fl;Wnt1Cre;p53-/- mutants to reduce apoptosis. The Ift88fl/fl;Wnt1Cre;p53-/- mice showed no excess bone formation, suggesting that the cells evading apoptosis by the presence of Ift88 in wild-type mice limit bone formation in maxillary development. On the other hand, the palatal cleft was retained in the Ift88fl/fl;Wnt1Cre;p53-/- mice, indicating that the excess bone formation or abnormal apoptosis was independent of the cleft palate phenotype in Ift88 mutant mice. CONCLUSIONS: Ift88 limits bone formation in the maxillary process by suppressing apoptosis.

DOI： 10.1016/j.archoralbio.2019.02.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The timing, location, and level of gene expression are crucial for normal organ development, because morphogenesis requires strict genetic control. MicroRNAs (miRNAs) are noncoding small single-stranded RNAs that play a critical role in regulating gene expression level. Although miRNAs are known to be involved in many biological events, the role of miRNAs in organogenesis is not fully understood. Mammalian eyelids fuse and separate during development and growth. In mice, failure of this process results in the eye-open at birth (EOB) phenotype. RESULTS: It has been shown that conditional deletion of mesenchymal Dicer (an essential protein for miRNA processing; Dicer fl/fl ;Wnt1Cre) leads to the EOB phenotype with full penetrance. Here, we identified that the up-regulation of Wnt signaling resulted in the EOB phenotype in Dicer mutants. Down-regulation of Fgf signaling observed in Dicer mutants was caused by an inverse relationship between Fgf and Wnt signaling. Shh and Bmp signaling were down-regulated as the secondary effects in Dicer fl/fl ;Wnt1Cre mice. Wnt, Shh, and Fgf signaling were also found to mediate the epithelial-mesenchymal interactions in eyelid development. CONCLUSIONS: miRNAs control eyelid development through Wnt. Developmental Dynamics 248:201-210, 2019. © 2019 Wiley Periodicals, Inc.

DOI： 10.1002/dvdy.10

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記述言語：日本語   出版者・発行元：新潟歯学会  

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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）  

Periodic patterning of iterative structures is diverse across the animal kingdom. Clarifying the molecular mechanisms involved in the formation of these structure helps to elucidate the process of organogenesis. Turing-type reaction-diffusion mechanisms have been shown to play a critical role in regulating periodic patterning in organogenesis. Palatal rugae are periodically patterned ridges situated on the hard palate of mammals. We have previously shown that the palatal rugae develop by a Turing-type reaction-diffusion mechanism, which is reliant upon Shh (as an inhibitor) and Fgf (as an activator) signaling for appropriate organization of these structures. The disturbance of Shh and Fgf signaling lead to disorganized palatal rugae. However, the mechanism itself is not fully understood. Here we found that Lrp4 (transmembrane protein) was expressed in a complementary pattern to Wise (a secreted BMP antagonist and Wnt modulator) expression in palatal rugae development, representing Lrp4 expression in developing rugae and Wise in the inter-rugal epithelium. Highly disorganized palatal rugae was observed in both Wise and Lrp4 mutant mice, and these mutants also showed the downregulation of Shh signaling, which was accompanied with upregulation of Fgf signaling. Wise and Lrp4 are thus likely to control palatal rugae development by regulating reaction-diffusion mechanisms through Shh and Fgf signaling. We also found that Bmp and Wnt signaling were partially involved in this mechanism.

DOI： 10.1371/journal.pone.0204126

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, intellectual disability, and multiple developmental abnormalities. Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with Kabuki syndrome having congenital absence of teeth, malocclusion, high-arched palate, micrognathia, and deviated tooth shape and size. Exome sequencing successfully identified that six patients were heterozygous for mutations in KMT2D, and one in KDM6A. Six were novel mutations, of which five were in KMT2D and one in KDM6A. They were truncating mutations including four frameshift deletions and two nonsense mutations. The predicted non-functional KMT2D and KDM6A proteins are expected to cause disease by haploinsufficiency. Our study expands oro-dental, medical, and mutational spectra associated with Kabuki syndrome. We also demonstrate for the first time that KMT2D and KDM6A are expressed in the dental epithelium of human tooth germs.

DOI： 10.7150/ijbs.23517

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The tongue is a critical organ, involved in functions such as speaking, swallowing, mastication, and degustation. Although Sox genes are known to play critical roles in many biological processes, including organogenesis, the expression of the Sox family members during tongue development remains unclear. We therefore performed a comparative in situ hybridization analysis of 17 Sox genes (Sox1-14, 17, 18, and 21) during murine tongue development. Sox2, 4, 6, 8, 9, 10, 11, 12, and 21 were found to be expressed in the tongue epithelium, whereas Sox2, 4-6, 8-11, 13, and 21 showed expression in the mesenchyme of the developing tongue. Expression of Sox1, 4, 6, 8-12, and 21 were observed in the developing tongue muscle. Sox5 and 13 showed expression only at E12, while Sox1 expression was observed only on E18. Sox6, 8, 9, and 12 showed expression at several stages. Although the expression of Sox2, 4, 10, 11, and 21 was detected during all the four stages of tongue development, their expression patterns differed among the stages. We thus identified a dynamic spatiotemporal expression pattern of the Sox genes during murine tongue development. To understand whether Sox genes are involved in the development of other craniofacial organs through similar roles to those in tongue development, we also examined the expression of Sox genes in eyelid primordia, which also contain epithelium, mesenchyme, and muscle. However, expression patterns and timing of Sox genes differed between tongue and eyelid development. Sox genes are thus related to organogenesis through different functions in each craniofacial organ.

DOI： 10.1155/2018/1601363

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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）  

DOI： 10.1002/DVDY.24427

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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  

Members of the Sox gene family play critical roles in many biological processes including organogenesis. We carried out comparative in situ hybridisation analysis of seventeen Sox genes (Sox1-14, 17, 18 and 21) during murine palatogenesis from initiation to fusion of the palatal shelves above the dorsal side of the tongue. At palatal shelf initiation (E12.5), the localized expression of six Sox genes (Sox2, 5, 6, 9,12 and 13) was observed in the shelves, whereas Sox4 and Sox11 showed ubiquitious expression. During the down growth of palatal shelves (E13.5), Sox4, Sox5, and Sox9 exhibited restricted expression to the interior side of the palatal shelves facing the tongue. Following elevation of the palatal shelves (E14.5), Sox2, Sox11 and Sox21 expression was present in the midline epithelial seam. We thus identify dynamic spatio-temporal expression of Sox gene family during the process of palatogenesis. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.gep.2016.05.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/0022034514556707

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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：UNIV BASQUE COUNTRY UPV-EHU PRESS  

Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox 1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development.

DOI： 10.1387/ijdb.150192ao

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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）  

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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：WILEY-BLACKWELL  

Background: Tooth development is highly regulated in mammals and it is regulated by networks of signaling pathways (e. g. Tnf, Wnt, Shh, Fgf and Bmp) whose activities are controlled by the balance between ligands, activators, inhibitors and receptors. The members of the R-spondin family are known as activators of Wnt signaling, and Lgr4, Lgr5, and Lgr6 have been identified as receptors for R-spondins. The role of R-spondin/Lgr signaling in tooth development, however, remains unclear. Results: We first carried out comparative in situ hybridization analysis of R-spondins and Lgrs, and identified their dynamic spatio-temporal expression in murine odontogenesis. R-spondin2 expression was found both in tooth germs and the tooth-less region, the diastema. We further examined tooth development in R-spondin2 mutant mice, and although molars and incisors exhibited no significant abnormalities, supernumerary teeth were observed in the diastema. Conclusions: R-spondin/Lgr signaling is thus involved in tooth development. Developmental Dynamics 243:844-851, 2014. (c) 2014 Wiley Periodicals, Inc.

DOI： 10.1002/dvdy.24124

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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  

Protein kinase A (PK A) plays critical roles in many biological processes including cell proliferation, cell differentiation, cellular metabolism and gene regulation. Mutation in PKA regulatory subunit, PRKAR1A has previously been identified in odontogenic myxomas, but it is unclear whether PKA is involved in tooth development. The aim of the present study was to assess the expression of alpha isoforms of PICA regulatory subunit (Prkar1a and Prkar2a) in mouse and human odontogenesis by in situ hybridization. PRKAR1A and PRKAR2A mRNA transcription was further confirmed in a human deciduous germ by qRT-PCR. Mouse Prkar1a and human PRKAR2A exhibited a dynamic spatio-temporal expression in tooth development, whereas neither human PRKAR1A nor mouse Prkar2a showed their expression in odontogenesis. These isoforms thus showed different expression pattern between human and mouse tooth germs. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.gep.2014.04.002

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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：OXFORD UNIV PRESS  

Polycystin 2 (Pkd2), which belongs to the transient receptor potential family, plays a critical role in development. Pkd2 is mainly localized in the primary cilia, which also function as mechanoreceptors in many cells that influence multiple biological processes including Ca-2 influx, chemical activity and signalling pathways. Mutations in many cilia proteins result in craniofacial abnormalities. Orofacial tissues constantly receive mechanical forces and are known to develop and grow through intricate signalling pathways. Here we investigate the role of Pkd2, whose role remains unclear in craniofacial development and growth. In order to determine the role of Pkd2 in craniofacial development, we located expression in craniofacial tissues and analysed mice with conditional deletion of Pkd2 in neural crest-derived cells, using Wnt1Cre mice. Pkd2 mutants showed many signs of mechanical trauma such as fractured molar roots, distorted incisors, alveolar bone loss and compressed temporomandibular joints, in addition to abnormal skull shapes. Significantly, mutants showed no indication of any of these phenotypes at embryonic stages when heads perceive no significant mechanical stress in utero. The results suggest that Pkd2 is likely to play a critical role in craniofacial growth as a mechanoreceptor. Pkd2 is also identified as one of the genes responsible for autosomal dominant polycystic kidney disease (ADPKD). Since facial anomalies have never been identified in ADPKD patients, we carried out three-dimensional photography of patient faces and analysed these using dense surface modelling. This analysis revealed specific characteristics of ADPKD patient faces, some of which correlated with those of the mutant mice.

DOI： 10.1093/hmg/ddt041

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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：SAGE PUBLICATIONS INC  

Teeth develop from interactions between embryonic oral epithelium and neural-crest-derived mesenchyme. These cells can be separated into single-cell populations and recombined to form normal teeth, providing a basis for bioengineering new teeth if suitable, non-embryonic cell sources can be identified. We show here that cells can be isolated from adult human gingival tissue that can be expanded in vitro and, when combined with mouse embryonic tooth mesenchyme cells, form teeth. Teeth with developing roots can be produced from this cell combination following transplantation into renal capsules. These bioengineered teeth contain dentin and enamel with ameloblast-like cells and rests of Malassez of human origin.

DOI： 10.1177/0022034513481041

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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：BIOMED CENTRAL LTD  

Background: The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke's pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke's pouch. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving the formation of the buccohypophyseal canal and their evolutionary significance.
Results: We show that Rathke's pouch is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polaris(fl/fl); Wnt1-Cre, Ofd1(-/-) and Kif3a(-/-) primary cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present with malformations of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1(-/-) mice. From an evolutionary perspective, persistence of the buccohypophyseal canal is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling.
Conclusion: These results provide insight into a poorly understood ancestral vertebrate structure. It appears that the opening of the buccohypophyseal canal depends upon Shh signaling and that modulation in this pathway most probably accounts for its persistence in phylogeny.

DOI： 10.1186/1741-7007-11-27

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DOI： 10.1186/1741-7007-11-27

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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：PUBLIC LIBRARY SCIENCE  

Hemidesmosomes are composed of intricate networks of proteins, that are an essential attachment apparatus for the integrity of epithelial tissue. Disruption leads to blistering diseases such as epidermolysis bullosa. Members of the Sox gene family show dynamic and diverse expression patterns during development and mutation analyses in humans and mice provide evidence that they play a remarkable variety of roles in development and human disease. Previous studies have established that the mouse mutant ragged-opossum (Ra-op) expresses a dominant-negative form of the SOX18 transcription factor that interferes with the function of wild type SOX18 and of the related SOXF-subgroup proteins SOX7 and -17. Here we show that skin and oral mucosa in homozygous Ra-op mice display extensive detachment of epithelium from the underlying mesenchymal tissue, caused by tearing of epithelial cells just above the plasma membrane due to hemidesmosome disruption. In addition, several hemidesmosome proteins expression were found to be dysregulated in the Ra-op mice. Our data suggest that SOXF transcription factors play a role in regulating formation of cytoplasmic plaque protein assembly, and that disrupted SOXF function results in epidermolysis bullosa-like skin phenotypes.

DOI： 10.1371/journal.pone.0043857

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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：WILEY-BLACKWELL  

Background: Tooth development is known to be mediated by the cross-talk between signaling pathways, including Shh, Fgf, Bmp, and Wnt. MicroRNAs (miRNAs) are 19- to 25-nt noncoding small single-stranded RNAs that negatively regulate gene expression by binding target mRNAs, which is believed to be important for the fine-tuning signaling pathways in development. To investigate the role of miRNAs in tooth development, we examined mice with either mesenchymal (Wnt1Cre/Dicerfl/fl) or epithelial (ShhCre/Dicerfl/fl) conditional deletion of Dicer, which is essential for miRNA processing. Results: By using a CD1 genetic background for Wnt1Cre/Dicerfl/fl, we were able to examine tooth development, because the mutants retained mandible and maxilla primordia. Wnt1Cre/Dicerfl/fl mice showed an arrest or absence of teeth development, which varied in frequency between incisors and molars. Extra incisor tooth formation was found in ShhCre/Dicerfl/fl mice, whereas molars showed no significant anomalies. Microarray and in situ hybridization analysis identified several miRNAs that showed differential expression between incisors and molars. Conclusion: In tooth development, miRNAs thus play different roles in epithelium and mesenchyme, and in incisors and molars. Developmental Dynamics 241:1465-1472, 2012. (c) 2012 Wiley Periodicals, Inc.

DOI： 10.1002/dvdy.23828

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objective: The purpose of this study was to subjectively evaluate the utility of newly developed denture placement and removal devices. Objective observations were also made to support the evidence.
Materials and method: Twenty-one subjects were instructed to place and remove their dentures with and without the devices. We evaluated the device based on a questionnaire. Objective observations were based on a 2-D image analysis. We analysed three factors: the time, the area and the circumference required to insert and remove the dentures.
Results: Image analysis showed that the effectiveness and ease with which the subject used the device significantly improved with practice. The questionnaire data showed that a majority of the subjects appreciated the device after the first and second time. While there was no significant decrease in time required to place and remove dentures even with the device, the area and circumference of the movement on 2-D images were significantly reduced.
Conclusion: In this study, the utility of denture placement and removal devices was evaluated both subjectively and objectively. Our data reveal that the device is effective in the elderly. Further minor improvement in the device might be required to increase its effectiveness.

DOI： 10.1111/j.1741-2358.2011.00547.x

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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：PERGAMON-ELSEVIER SCIENCE LTD  

Objective: Tongue papillae are critical organs in mastication. There are four different types of tongue papillae; fungiform, circumvallate, foliate, and filiform papillae. Unlike the other three taste papillae, non-gustatory papillae, filiform papillae cover the entire dorsal surface of the tongue and are important structures for the mechanical stress of sucking. Filiform papillae are further classified into two subtypes with different morphologies, depending on their location on the dorsum of the tongue. The filiform papillae at the intermolar eminence have pointed tips, whereas filiforrn papillae with rounded tips are found in other regions (anterior tongue). It remains unknown how the shape of each type of filiform papillae are determined during their development. Bmp signalling pathway has been known to regulate mechanisms that determine the shapes of many ectodermal organs. The aim of this study was to investigate the role of Bmp signalling in filiform papillae development.
Design: Comparative in situ hybridization analysis of six Bmps (Bmp2-Bmp7) and two Bmpr genes (Bmpr1a and Bmpr1b) were carried out in filiform papillae development. We further examined tongue papillae in mice over-expressing Noggin under the keratin14 promoter (K14-Noggin).
Results: We identified a dynamic temporo-spatial expression of Bmps in filiform papillae development. The K14-Noggin mice showed pointed filiform papillae in regions of the tongue normally occupied by the rounded type.
Conclusions: Bmp signalling thus regulates the shape of filiform papillae. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2011.11.014

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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：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Thickening and the subsequent invagination of the epithelium are an important initial step in Ectodermal organ development. Ikk alpha has been shown to play a critical role in controlling epithelial growth, since Ikk alpha mutant mice show protrusions (evaginations) of incisor tooth, whisker and hair follicle epithelium rather than invagination. We show here that mutation of the Interferon regulatory factor (11) family, Irf6 also results in evagination of incisor epithelium. In common with Ikk alpha mutants, Irf6 mutant evagination occurs in a NF-kappa B-independent manner and shows the same molecular changes as those in Ikk alpha mutants. Irf6 thus also plays a critical role in regulating epithelial invagination. In addition, we also found that canonical Wnt signaling is upregulated in evaginated incisor epithelium of both Ikk alpha and Irf6 mutant embryos. (C) 2012 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ydbio.2012.02.009

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PubMed

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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：SPRINGER  

We examined the influence of rheological/textural properties and volumes of test foods on the sensory and motor aspects of swallowing in healthy young adults. Three test foods differing in thickening agent concentration (0.0, 1.5, and 3.0%) were prepared and delivered in different volumes (similar to 3, similar to 5, and similar to 7 ml) to subjects seated on a chair. Viscosity analyses of the 1.5 and 3.0% test foods revealed that they behaved as non-Newtonian fluids and were thixotropic. The 1.5% test food differed from the 3.0% test food in its textural properties (hardness, cohesiveness, and adhesiveness). As determined by a linear model equation method, the thickening agent concentration affected the scores of all six sensory evaluation questions that were answered by the subjects, which suggests that the concentration affected the food properties being evaluated. Consistent with previous reports, thickening agent concentration and test food volume also affected some durational parameters of laryngeal (recorded by a piezoelectric sensor) and suprahyoid muscle (recorded on an electromyogram) motor activity. However, thickening agent concentration and test food volume did not affect the single amplitude parameter of the electromyogram that was measured. The thixotropic property of foods can affect the motor aspect of oropharyngeal swallowing as well as the sensory aspect.

DOI： 10.1007/s00455-009-9243-y

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PubMed

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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：日本家政学会  

嚥下しやすい食品の要因を評価するために,物性がゼラチンに近いといわれている即溶性低強度寒天(LGSA:low-gel-strength agar)を試料として用い,物性測定はクリープメーター(山電製・日本)を使用して研究をおこなった.今回の結果では,甘味,塩味,酸味を呈する試料の硬さが濃度の変化に相応して,無味の試料にくらべて高いことが示唆された.さらにLGSAを用いて嚥下における総合的官能評価[濃度(硬さ)・味・量]を20歳代の健常な学生群と70～80歳代の健常な高齢者群に対しておこなったところ,健常な学生群は1.1%が好ましい濃度(硬さ)であり,さらに味では甘味が,量に関しては5.0gが口腔内においてもっとも嚥下しやすいと評価した.一方健常な高齢者群は甘味のみが嚥下しやすいと評価した.これらのことから,食品の物性を含むいくつかの要因が嚥下にたいして関与していることが示唆された.

DOI： 10.11428/jhej.60.133

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記述言語：日本語  

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CiNii Books

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記述言語：日本語  

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CiNii Books

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記述言語：日本語  

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)歯科基礎医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本顎関節学会  

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開催年月日： 2023年4月

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記述言語：英語   会議種別：口頭発表（一般）  

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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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開催年月日： 2009年11月

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開催年月日： 2009年11月

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開催年月日： 2009年11月

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開催年月日： 2009年9月

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開催年月日： 2009年9月

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開催年月日： 2009年7月

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開催年月日： 2009年7月

会議種別：口頭発表（一般）  

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開催年月日： 2009年6月

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2009年6月

会議種別：口頭発表（一般）  

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会議種別：口頭発表（一般）  

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記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

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会議種別：口頭発表（一般）  

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会議種別：口頭発表（一般）  

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会議種別：口頭発表（一般）  

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会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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