Title: FAF1, a Gene that Is Disrupted in Cleft Palate and Has Conserved Function in Zebrafish
Authors: Ghassibe-Sabbagh, Michella
Desmyter, Laurence
Langenberg, Tobias
Claes, Filip
Boute, Odile
Bayet, Bénédicte
Pellerin, Philippe
Hermans, Karlien
Backx, Liesbeth
Mansilla, Maria Adela
Imoehl, Sandra
Nowak, Stefanie
Ludwig, Kerstin U
Baluardo, Carlotta
Ferrian, Melissa
Mossey, Peter A
Noethen, Markus
Dewerchin, Mieke
François, Geneviève
Revencu, Nicole
Vanwijck, Romain
Hecht, Jacqueline
Mangold, Elisabeth
Murray, Jeffrey
Rubini, Michele
Vermeesch, Joris
Poirel, Hélène A
Carmeliet, Peter
Vikkula, Miikka # ×
Issue Date: Feb-2011
Publisher: American Society of Human Genetics
Series Title: American Journal of Human Genetics vol:88 issue:2 pages:150-161
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.
ISSN: 0002-9297
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Vesalius Research Centre (-)
Clinical Genetics
Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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