Fgf10 is essential for limb and lung formation

Nat Genet. 1999 Jan;21(1):138-41. doi: 10.1038/5096.

Abstract

The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis. In particular, Fgf10 is predicted to function as a regulator of brain, lung and limb development on the basis of its spatiotemporal expression pattern in the developing embryo. To define the role of Fgf10, we generated Fgf10-deficient mice. Fgf10-/- mice died at birth due to the lack of lung development. Trachea was formed, but subsequent pulmonary branching morphogenesis was disrupted. In addition, mutant mice had complete truncation of the fore- and hindlimbs. In Fgf10-/- embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected. Analysis of the expression of marker genes in the mutant limb buds indicated that the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) did not form. Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / genetics
  • Extremities / embryology*
  • Female
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / physiology*
  • Hedgehog Proteins
  • Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins
  • Lung / embryology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteins / genetics
  • Proto-Oncogene Proteins / genetics
  • T-Box Domain Proteins*
  • Trans-Activators*
  • Transcription Factors / genetics
  • Wnt Proteins
  • Wnt2 Protein

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Fgf10 protein, mouse
  • Fgf8 protein, mouse
  • Fibroblast Growth Factor 10
  • Hedgehog Proteins
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lmx1a protein, mouse
  • Proteins
  • Proto-Oncogene Proteins
  • T-Box Domain Proteins
  • T-box transcription factor 5
  • Tbx4 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Wnt2 Protein
  • Wnt7a protein, mouse
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors