研究腭裂起源的科学家可能发现了一个与这种病的发育阶段有关的遗传靶标。David Ornitz及其同事分析了成纤维细胞生长因子受体（FGFR）基因，它与腭裂的形成有关。
此前的研究已经表明腭裂的表现型可能源于FGFR的多遗传突变。这组作者发现，FGFR的单个突变――称为“失去功能”，它让FGFR受体失去活性――可能导致与一个“获得功能”突变――它让这种受体获得增加或不正常的功能――相同的表现型。这组科学家研究了有一种常见的“获得功能”突变的小鼠模型，结果发现了有这种突变受体的小鼠表现出了成纤维细胞生长因子受体信号传导的改变、细胞生长异常以及细胞外基质（细胞外的支架）的变化。这些实验小鼠的腭延长减少了，而腭架抬升延迟了，这导致了腭裂。这组作者说，尽管腭裂具有不同的遗传起源，针对这种病的这些发育阶段可以提供治疗腭裂的策略。
生物谷推荐原始出处：
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.
