Yannakoudakis Basil Z, Liu Karen J
Department of Craniofacial Development and Stem Cell Biology; King's College London; London, UK.
Rare Dis. 2013 Nov 11;1:e27109. doi: 10.4161/rdis.27109. eCollection 2013.
Congenital skeletal anomalies are rare disorders, with a subset affecting both the cranial and appendicular skeleton. Two categories, craniosynostosis syndromes and chondrodysplasias, frequently result from aberrant regulation of the fibroblast growth factor (FGF) signaling pathway. Our recent work has implicated FGF signaling in a third category: ciliopathic skeletal dysplasias. In this work, we have used mouse mutants in two ciliopathy genes, Fuzzy (Fuz) and orofacial digital syndrome-1 (Ofd-1), to demonstrate increase in Fgf8 gene expression during critical stages of embryogenesis. While the mechanisms underlying FGF dysregulation differ in the different syndromes, our data raise the possibility that convergence on FGF signal transduction may underlie a wide range of skeletal anomalies. Here, we provide additional evidence of the skeletal phenotypes from the Fuz mouse model and highlight similarities between human ciliopathies and FGF-related syndromes.
先天性骨骼异常是罕见疾病，其中一部分会同时影响颅骨和附属骨骼。颅缝早闭综合征和软骨发育不全这两类疾病，通常是由成纤维细胞生长因子（FGF）信号通路的异常调控导致的。我们最近的研究表明，FGF信号传导与第三类疾病有关：纤毛病性骨骼发育不良。在这项研究中，我们使用了两个纤毛病基因（Fuzzy，简称Fuz和口面指综合征1，简称Ofd-1）的小鼠突变体，来证明在胚胎发育的关键阶段Fgf8基因表达增加。虽然不同综合征中FGF失调的机制有所不同，但我们的数据表明，FGF信号转导的共同作用可能是多种骨骼异常的基础。在这里，我们提供了来自Fuz小鼠模型的骨骼表型的更多证据，并强调了人类纤毛病与FGF相关综合征之间的相似性。
