Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia

Kurosaka, Hiroshi; Wang, Qi; Sandell, Lisa; Yamashiro, Takashi; Trainor, Paul A.

doi:https://doi.org/10.1093/hmg/ddx031

Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia

Kurosaka, Hiroshi; Wang, Qi; Sandell, Lisa et al.

Human Molecular Genetics, 2017, 26(7), 1268-1279

アクセス数:35件（2026-02-15 23:28 集計）

固定URL: https://hdl.handle.net/11094/103556

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タイトル	Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia
著者	NRID 1000020509369 1000020509369 ORCID 0000-0002-8956-5467 0000-0002-8956-5467 researchmap permalink kurosakahiroshi kurosakahiroshi Scopus Author ID 11839162500 11839162500 著者名 Kurosaka, Hiroshi
	著者名 Wang, Qi
	著者名 Sandell, Lisa
	NRID 1000070294428 1000070294428 ORCID 0000-0002-4419-9643 0000-0002-4419-9643 researchmap permalink read0051793 read0051793 Scopus Author ID 55416765600 55416765600 著者名 Yamashiro, Takashi
	著者名 Trainor, Paul A.
内容	Kurosaka H., Wang Q., Sandell L., et al. Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia. Human Molecular Genetics 26, 1268 (2017); https://doi.org/10.1093/hmg/ddx031.
抄録	Craniofacial development is a complex process that involves sequential growth and fusion of the facial prominences. When these processes fail, congenital craniofacial anomalies can occur. For example, choanal atresia (CA) is a congenital craniofacial anomaly in which the connection between the nasal airway and nasopharynx is completely blocked. CA occurs in approximately 1/5000 live births and is a frequent component of congenital disorders such as CHARGE, Treacher Collins, Crouzon and Pfeiffer syndromes. However, the detailed cellular and molecular mechanisms underpinning the etiology and pathogenesis of CA remain elusive. In this study, we discovered that mice with mutations in retinol dehydrogenase 10 (Rdh10), which perturbs Vitamin A metabolismand retinoid signaling, exhibit fully penetrant CA. Interestingly, we demonstrate Rdh10 is specifically required in non-neural crest cells prior to E10.5 for proper choanae formation, and that in the absence of Rdh10, Fgf8 is ectopically expressed in the nasal fin. Furthermore, we found that defects in choanae development are associated with decreased cell proliferation and increased cell death in the epithelium of the developing nasal cavity, which retards invagination of the nasal cavity, and thus appears to contribute to the pathogenesis of CA. Taken together, our findings demonstrate that RDH10 is essential during the early stages of facial morphogenesis for the formation of a functional nasal airway, and furthermore establish Rdh10 mutant mice as an important model system to study CA.
出版者	Oxford University Press
収録物名	Human Molecular Genetics
巻(号)	26(7)
ページ	1268-1279
刊行年月	2017-02-07
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103556
PISSN	09646906
eISSN	14602083
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1093/hmg/ddx031
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Human Molecular Genetics. 2017, 26(7), p. 1268-1279
DC.title	Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia
DC.creator	Kurosaka, Hiroshi
	Wang, Qi
	Sandell, Lisa
	Yamashiro, Takashi
	Trainor, Paul A.
DC.publisher	Oxford University Press
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2017-02-07
DC.identifier	https://doi.org/10.1093/hmg/ddx031
DC.description	Kurosaka H., Wang Q., Sandell L., et al. Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia. Human Molecular Genetics 26, 1268 (2017); https://doi.org/10.1093/hmg/ddx031.
DCTERMS.abstract	Craniofacial development is a complex process that involves sequential growth and fusion of the facial prominences. When these processes fail, congenital craniofacial anomalies can occur. For example, choanal atresia (CA) is a congenital craniofacial anomaly in which the connection between the nasal airway and nasopharynx is completely blocked. CA occurs in approximately 1/5000 live births and is a frequent component of congenital disorders such as CHARGE, Treacher Collins, Crouzon and Pfeiffer syndromes. However, the detailed cellular and molecular mechanisms underpinning the etiology and pathogenesis of CA remain elusive. In this study, we discovered that mice with mutations in retinol dehydrogenase 10 (Rdh10), which perturbs Vitamin A metabolismand retinoid signaling, exhibit fully penetrant CA. Interestingly, we demonstrate Rdh10 is specifically required in non-neural crest cells prior to E10.5 for proper choanae formation, and that in the absence of Rdh10, Fgf8 is ectopically expressed in the nasal fin. Furthermore, we found that defects in choanae development are associated with decreased cell proliferation and increased cell death in the epithelium of the developing nasal cavity, which retards invagination of the nasal cavity, and thus appears to contribute to the pathogenesis of CA. Taken together, our findings demonstrate that RDH10 is essential during the early stages of facial morphogenesis for the formation of a functional nasal airway, and furthermore establish Rdh10 mutant mice as an important model system to study CA.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	103556
citation_title	Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia
citation_author	Kurosaka, Hiroshi
	Wang, Qi
	Sandell, Lisa
	Yamashiro, Takashi
	Trainor, Paul A.
citation_publisher	Oxford University Press
citation_language	英語
citation_date	2017-02-07
citation_journal_title	Human Molecular Genetics
citation_volume	26
citation_issue	7
citation_firstpage	1268
citation_lastpage	1279
citation_doi	https://doi.org/10.1093/hmg/ddx031
citation_public_url	https://hdl.handle.net/11094/103556

Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia

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