Functions of FGF signalling from the apical ectodermal ridge in limb development

Nature. 2002 Aug 1;418(6897):501-8. doi: 10.1038/nature00902.

Abstract

To determine the role of fibroblast growth factor (FGF) signalling from the apical ectodermal ridge (AER), we inactivated Fgf4 and Fgf8 in AER cells or their precursors at different stages of mouse limb development. We show that FGF4 and FGF8 regulate cell number in the nascent limb bud and are required for survival of cells located far from the AER. On the basis of the skeletal phenotypes observed, we conclude that these functions are essential to ensure that sufficient progenitor cells are available to form the normal complement of skeletal elements, and perhaps other limb tissues. In the complete absence of both FGF4 and FGF8 activities, limb development fails. We present a model to explain how the mutant phenotypes arise from FGF-mediated effects on limb bud size and cell survival.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Body Patterning*
  • Cell Count
  • Cell Division
  • Ectoderm / cytology
  • Ectoderm / metabolism*
  • Female
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Forelimb / cytology
  • Forelimb / embryology*
  • Forelimb / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Hindlimb / abnormalities
  • Hindlimb / cytology
  • Hindlimb / embryology*
  • Hindlimb / metabolism
  • Limb Buds / cytology
  • Limb Buds / metabolism
  • Male
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / embryology
  • Muscle, Skeletal / metabolism
  • Phenotype
  • Signal Transduction*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Time Factors

Substances

  • Fgf8 protein, mouse
  • fibroblast growth factor 14
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors