Abstract：
:Cranial neural crest (CNC) is a multipotent migratory cell population that gives rise to most of the craniofacial bones. An intricate network mediates CNC formation, epithelial-mesenchymal transition, migration along distinct paths, and differentiation. Errors in these processes lead to craniofacial abnormalities, including cleft lip and palate. Clefts are the most common congenital craniofacial defects. Patients have complications with feeding, speech, hearing, and dental and psychological development. Affected by both genetic predisposition and environmental factors, the complex etiology of clefts remains largely unknown. Here we show that Fas-associated factor-1 (FAF1) is disrupted and that its expression is decreased in a Pierre Robin family with an inherited translocation. Furthermore, the locus is strongly associated with cleft palate and shows an increased relative risk. Expression studies show that faf1 is highly expressed in zebrafish cartilages during embryogenesis. Knockdown of zebrafish faf1 leads to pharyngeal cartilage defects and jaw abnormality as a result of a failure of CNC to differentiate into and express cartilage-specific markers, such as sox9a and col2a1. Administration of faf1 mRNA rescues this phenotype. Our findings therefore identify FAF1 as a regulator of CNC differentiation and show that it predisposes humans to cleft palate and is necessary for lower jaw development in zebrafish.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Ghassibe-Sabbagh M,Desmyter L,Langenberg T,Claes F,Boute O,Bayet B,Pellerin P,Hermans K,Backx L,Mansilla MA,Imoehl S,Nowak S,Ludwig KU,Baluardo C,Ferrian M,Mossey PA,Noethen M,Dewerchin M,François G,Revencu N,Vanwdoi
10.1016/j.ajhg.2011.01.003subject
Has Abstractpub_date
2011-02-11 00:00:00pages
150-61issue
2eissn
0002-9297issn
1537-6605pii
S0002-9297(11)00004-8journal_volume
88pub_type
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302020
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journal_title：American journal of human genetics
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doi：10.1086/320112
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
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journal_title：American journal of human genetics
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doi：10.1086/380311
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
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journal_title：American journal of human genetics
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doi：
更新日期：1991-08-01 00:00:00
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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