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Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development
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SYSNO ASEP 0485269 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development Author(s) Celá, Petra (UZFG-Y) RID
Hampl, Marek (UZFG-Y) ORCID
Shylo, N. (US)
Christopher, K. J. (US)
Kavková, M. (CZ)
Landová, Marie (UZFG-Y) ORCID
Zikmund, T. (CZ)
Weatherbee, S. D. (US)
Kaiser, J. (CZ)
Buchtová, Marcela (UZFG-Y) RID, ORCIDSource Title Journal of Dental Research. - : Sage - ISSN 0022-0345
Roč. 97, č. 1 (2018), s. 108-117Number of pages 10 s. Language eng - English Country US - United States Keywords craniofacial anomalies ; growth/development ; mineralized tissue/development ; orofacial clefts ; cell signaling Subject RIV FF - HEENT, Dentistry OECD category Dentistry, oral surgery and medicine R&D Projects GB14-37368G GA ČR - Czech Science Foundation (CSF) EF15_003/0000460 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UZFG-Y - RVO:67985904 UT WOS 000418548700014 EID SCOPUS 85038833183 DOI 10.1177/0022034517732538 Annotation A broad spectrum of human diseases called ciliopathies is caused by defective primary cilia morphology or signal transduction. The primary cilium is a solitary organelle that responds to mechanical and chemical stimuli from extracellular and intracellular environments. Transmembrane protein 107 (TMEM107) is localized in the primary cilium and is enriched at the transition zone where it acts to regulate protein content of the cilium. Mutations in TMEM107 were previously connected with oral-facial-digital syndrome, MeckelGruber syndrome, and Joubert syndrome exhibiting a range of ciliopathic defects. Here, we analyze a role of Tmem107 in craniofacial development with special focus on palate formation, using mouse embryos with a complete knockout of Tmem107. Tmem107(-/-) mice were affected by a broad spectrum of craniofacial defects, including shorter snout, expansion of the facial midline, cleft lip, extensive exencephaly, and microphthalmia or anophthalmia. External abnormalities were accompanied by defects in skeletal structures, including ossification delay in several membranous bones and enlargement of the nasal septum or defects in vomeronasal cartilage. Alteration in palatal shelves growth resulted in clefting of the secondary palate. Palatal defects were caused by increased mesenchymal proliferation leading to early overgrowth of palatal shelves followed by defects in their horizontalization. Moreover, the expression of epithelial stemness marker SOX2 was altered in the palatal shelves of Tmem107(-/-) animals, and differences in mesenchymal SOX9 expression demonstrated the enhancement of neural crest migration. Moreover, Shh and Gli1 expression was increased in Tmem107(-/-) animals as shown by in situ hybridization. Thus, TMEM107 is essential for proper head development, and defective TMEM107 function leads to ciliary morphology disruptions in a region-specific manner, which may explain the complex mutant phenotype. Workplace Institute of Animal Physiology and Genetics Contact Jana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554 Year of Publishing 2019
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