Common skeletal features in rare diseases: New links between ciliopathies and FGF-related syndromes.
Common skeletal features in rare diseases: New links between ciliopathies and FGF-related syndromes.
复制标题
DOI：
10.4161/rdis.27109
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Liu KJ
中科院分区：
文献类型：
--
作者：
Yannakoudakis BZ;Liu KJ
先天性骨骼异常是一种罕见的疾病，有一个子集影响到颅和approximular骨骼。两类，颅缝早闭综合征和软骨发育不良，经常由成纤维细胞生长因子（FGF）信号通路的异常调节引起。我们最近的工作涉及第三类FGF信号传导：纤毛病骨骼发育不良。在这项工作中，我们使用了小鼠突变体在两个纤毛病变基因，模糊（Fuz）和orofacial数字综合征-1（OFD-1），以证明在胚胎发生的关键阶段FGF 8基因表达的增加。虽然潜在的FGF失调的机制在不同的综合征不同，我们的数据提出的可能性，FGF信号转导的收敛可能是一个广泛的骨骼异常的基础。在这里，我们提供了额外的证据，骨骼表型从Fuz小鼠模型和突出人类纤毛病变和FGF相关综合征之间的相似性。
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.