Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth

Kai Yu, Jingsong Xu, Zhonghao Liu, Drazen Sosic, Jiansu Shao, Eric N. Olson, Dwight A. Towler, David M. Ornitz

Research output: Contribution to journalArticle

459 Scopus citations

Abstract

Human craniosynostosis syndromes, resulting from activating or neomorphic mutations in fibroblast growth factor receptor 2 (FGFR2), underscore an essential role for FGFR2 signaling in skeletal development. Embryos harboring homozygous null mutations in FGFR2 die prior to skeletogenesis. To address the role of FGFR2 in normal bone development, a conditional gene deletion approach was adopted. Homologous introduction of cre recombinase into the Dermo1 (Twist2) gene locus resulted in robust expression of CRE in mesenchymal condensations giving rise to both osteoblast and chondrocyte lineages. Inactivation of a floxed Fgfr2 allele with Dermo1-cre resulted in mice with skeletal dwarfism and decreased bone density. Although differentiation of the osteoblast lineage was not disturbed, the proliferation of osteoprogenitors and the anabolic function of mature osteoblasts were severely affected.

Original languageEnglish (US)
Pages (from-to)3063-3074
Number of pages12
JournalDevelopment
Volume130
Issue number13
DOIs
StatePublished - Jul 1 2003

Keywords

  • Chondrocyte
  • Conditional gene deletion
  • Cre recombinase
  • Dermo1
  • Endochondral bone growth
  • FGF
  • FGF receptor
  • FGFR2
  • Fibroblast growth factor
  • Ossification
  • Osteoblast
  • Twist2

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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