Common skeletal features in rare diseases: New links between ciliopathies and FGF-related syndromes

TY - JOUR

T1 - Common skeletal features in rare diseases

T2 - New links between ciliopathies and FGF-related syndromes

AU - Yannakoudakis, Basil

AU - Liu, Karen

PY - 2013/11/11

Y1 - 2013/11/11

N2 - 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.

AB - 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.

KW - FGF

KW - Cilia

KW - ciliopathy

KW - skeletal dysplasia

U2 - 10.4161/rdis.27109

DO - 10.4161/rdis.27109

M3 - Article

VL - 1

JO - Rare Diseases

JF - Rare Diseases

IS - 1

M1 - e27109

ER -