研究腭裂起源的科學(xué)家可能發(fā)現(xiàn)了一個(gè)與這種病的發(fā)育階段有關(guān)的遺傳靶標(biāo),。David Ornitz及其同事分析了成纖維細(xì)胞生長(zhǎng)因子受體（FGFR）基因，它與腭裂的形成有關(guān),。
此前的研究已經(jīng)表明腭裂的表現(xiàn)型可能源于FGFR的多遺傳突變。這組作者發(fā)現(xiàn),，F(xiàn)GFR的單個(gè)突變——稱為“失去功能”,，它讓FGFR受體失去活性——可能導(dǎo)致與一個(gè)“獲得功能”突變——它讓這種受體獲得增加或不正常的功能——相同的表現(xiàn)型。這組科學(xué)家研究了有一種常見(jiàn)的“獲得功能”突變的小鼠模型,，結(jié)果發(fā)現(xiàn)了有這種突變受體的小鼠表現(xiàn)出了成纖維細(xì)胞生長(zhǎng)因子受體信號(hào)傳導(dǎo)的改變,、細(xì)胞生長(zhǎng)異常以及細(xì)胞外基質(zhì)（細(xì)胞外的支架）的變化。這些實(shí)驗(yàn)小鼠的腭延長(zhǎng)減少了,，而腭架抬升延遲了,，這導(dǎo)致了腭裂。這組作者說(shuō),，盡管腭裂具有不同的遺傳起源，針對(duì)這種病的這些發(fā)育階段可以提供治療腭裂的策略,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS February 1, 2010, doi: 10.1073/pnas.0913985107
Analysis of a gain-of-function FGFR2 Crouzon mutation provides evidence of loss of function activity in the etiology of cleft palate
Alison K. Snyder-Warwicka,b, Chad A. Perlyna,b,c, Jing Pand, Kai Yub, Lijuan Zhangd, and David M. Ornitzb,1
aDivision of Plastic Surgery and
bDepartments of Developmental Biology and
dPathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; and
cDivision of Plastic Surgery, Miami Children’s Hospital, Miami, FL 33155
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.
