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PMID:21295280

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Citation

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, Vanwijck, R, Hecht, J, Mangold, E, Murray, J, Rubini, M, Vermeesch, JR, Poirel, HA, Carmeliet, P and Vikkula, M (2011) FAF1, a gene that is disrupted in cleft palate and has conserved function in zebrafish. Am. J. Hum. Genet. 88:150-61

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.

Links

PubMed PMC3035709 Online version:10.1016/j.ajhg.2011.01.003

Keywords

Adaptor Proteins, Signal Transducing/genetics; Animals; Animals, Genetically Modified; Blotting, Western; Cartilage/metabolism; Cell Differentiation; Cleft Palate/etiology; Cleft Palate/pathology; Embryo, Nonmammalian/cytology; Embryo, Nonmammalian/metabolism; Female; Gene Expression Regulation, Developmental; Humans; In Situ Hybridization, Fluorescence; Male; Mutation/genetics; Neural Crest/metabolism; Neural Crest/pathology; Pedigree; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction; Zebrafish/genetics; Zebrafish/growth & development; Zebrafish Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:B0UXY9

involved_in

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-2

P

Seeded From UniProt

complete

DANRE:B0UXY9

involved_in

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-1

P

Seeded From UniProt

complete

DANRE:B0UXY9

involved_in

GO:0060037: pharyngeal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:B0UXY9

involved_in

GO:0060037: pharyngeal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-1

P

Seeded From UniProt

complete

DANRE:Q7ZUK8

involved_in

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-2

P

Seeded From UniProt

complete

DANRE:Q7ZUK8

involved_in

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-1

P

Seeded From UniProt

complete

DANRE:Q7ZUK8

involved_in

GO:0060037: pharyngeal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q7ZUK8

involved_in

GO:0060037: pharyngeal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-1

P

Seeded From UniProt

complete

DANRE:Q8JGN2

involved_in

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-2

P

Seeded From UniProt

complete

DANRE:Q8JGN2

involved_in

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-1

P

Seeded From UniProt

complete

DANRE:Q8JGN2

involved_in

GO:0060037: pharyngeal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q8JGN2

involved_in

GO:0060037: pharyngeal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110221-1

P

Seeded From UniProt

complete


See also

References

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