Analysis of a gain-of-function FGFR2 Crouzon mutation provides evidence of loss of function activity in the etiology of cleft palate. Proc Natl Acad Sci U S A 2010 Feb 09;107(6):2515-20
Date
02/06/2010Pubmed ID
20133659Pubmed Central ID
PMC2823872DOI
10.1073/pnas.0913985107Scopus ID
2-s2.0-77249092531 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
Cleft palate is a common birth defect in humans and is a common phenotype associated with syndromic mutations in fibroblast growth factor receptor 2 (Fgfr2). Cleft palate occurred in nearly all mice homozygous for the Crouzon syndrome mutation C342Y in the mesenchymal splice form of Fgfr2. Mutant embryos showed delayed palate elevation, stage-specific biphasic changes in palate mesenchymal proliferation, and reduced levels of mesenchymal glycosaminoglycans (GAGs). Reduced levels of feedback regulators of FGF signaling suggest that this gain-of-function mutation in FGFR2 ultimately resembles loss of FGF function in palate mesenchyme. Knowledge of how mesenchymal FGF signaling regulates palatal shelf development may ultimately lead to pharmacological approaches to reduce cleft palate incidence in genetically predisposed humans.
Author List
Snyder-Warwick AK, Perlyn CA, Pan J, Yu K, Zhang L, Ornitz DMMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cell Proliferation
Cleft Palate
Embryo, Mammalian
Female
Gene Expression Regulation, Developmental
Genetic Predisposition to Disease
Glycosaminoglycans
In Situ Hybridization
Male
Mice
Mice, Knockout
Mutation
Palate
Receptor, Fibroblast Growth Factor, Type 2
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Time Factors
Tissue Culture Techniques