Journal article
FAF1, a Gene that Is Disrupted in Cleft Palate and Has Conserved Function in Zebrafish
American journal of human genetics, Vol.88(2), pp.150-161
2011
DOI: 10.1016/j.ajhg.2011.01.003
PMCID: PMC3035709
PMID: 21295280
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.
Details
- Title: Subtitle
- FAF1, a Gene that Is Disrupted in Cleft Palate and Has Conserved Function in Zebrafish
- Creators
- Michella Ghassibe-Sabbagh - Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, 1200 Brussels, BelgiumLaurence Desmyter - Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, 1200 Brussels, BelgiumTobias Langenberg - Vesalius Research Center, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumFilip Claes - Vesalius Research Center, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumOdile Boute - Centre de Génétique, Centre Hospitalier Universitaire de Lille, 59037 Lille, FranceBénédicte Bayet - Centre Labiopalatin, Service de Chirurgie Plastique, Cliniques Universitaires Saint-Luc, 1200 Brussels, BelgiumPhilippe Pellerin - Service de Chirurgie Plastique et Reconstructive, Centre Hospitalier Universitaire de Lille, 59037 Lille, FranceKarlien Hermans - Vesalius Research Center, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumLiesbeth Backx - Center for Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumMaria Adela Mansilla - Department of Pediatrics, University of Iowa, Iowa City, 52242 IA, USASandra Imoehl - Department of Pediatrics, University of Iowa, Iowa City, 52242 IA, USAStefanie Nowak - Institute of Human Genetics, University of Bonn, 53012 Bonn, GermanyKerstin U Ludwig - Department of Genomics, Life and Brain Center, University of Bonn, 53012 Bonn, GermanyCarlotta Baluardo - Medical Genetics Unit, Department of Experimental and Diagnostic Medicine, University of Ferrara, 44121 Ferrara, ItalyMelissa Ferrian - Medical Genetics Unit, Department of Experimental and Diagnostic Medicine, University of Ferrara, 44121 Ferrara, ItalyPeter A Mossey - Orthodontic Unit, Dental Hospital & School, University of Dundee, Dundee DD1 4HR, Scotland, UKMarkus Noethen - Institute of Human Genetics, University of Bonn, 53012 Bonn, GermanyMieke Dewerchin - Vesalius Research Center, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumGeneviève François - Centre Labiopalatin, Service de Chirurgie Plastique, Cliniques Universitaires Saint-Luc, 1200 Brussels, BelgiumNicole Revencu - Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, 1200 Brussels, BelgiumRomain Vanwijck - Centre Labiopalatin, Service de Chirurgie Plastique, Cliniques Universitaires Saint-Luc, 1200 Brussels, BelgiumJacqueline Hecht - Department of Pediatrics, University of Texas Medical School at Houston, Houston, Texas 77030, USAElisabeth Mangold - Institute of Human Genetics, University of Bonn, 53012 Bonn, GermanyJeffrey Murray - Department of Pediatrics, University of Iowa, Iowa City, 52242 IA, USAMichele Rubini - Medical Genetics Unit, Department of Experimental and Diagnostic Medicine, University of Ferrara, 44121 Ferrara, ItalyJoris R Vermeesch - Center for Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumHélène A Poirel - Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, 1200 Brussels, BelgiumPeter Carmeliet - Vesalius Research Center, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumMiikka Vikkula - Laboratory of Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.88(2), pp.150-161
- DOI
- 10.1016/j.ajhg.2011.01.003
- PMID
- 21295280
- PMCID
- PMC3035709
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2011
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Iowa Institute of Human Genetics
- Record Identifier
- 9984025363902771
Metrics
31 Record Views