A splice variant of CD44 expressed in the apical ectodermal ridge presents fibroblast growth factors to limb mesenchyme and is required for limb outgrowth

Larry Sherman, David Wainwright, Helmut Ponta, Peter Herrlich

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Signals from the apical ectodermal ridge (AER) of the developing vertebrate limb, including fibroblast growth factor-8 (FGF-8), can maintain limb mesenchymal cells in a proliferative state. We report here that a specific CD44 splice variant is crucial for the proliferation of these mesenchymal cells. Epitopes carried by this variant colocalize temporally and spatially with FGF-8 in the AER throughout early limb development. A splice variant containing the same sequences expressed on model cells binds both FGF-4 and FGF-8 and stimulates mesenchymal cells in vitro. When applied to the AER, an antibody against a specific CD44 epitope blocks FGF presentation and inhibits limb outgrowth. Therefore, CD44 is necessary for limb development and functions in a novel growth factor presentation mechanism likely relevant in other physiological and pathological situations where a cell surface protein presents a signaling molecule to a neighboring cell.

Original languageEnglish (US)
Pages (from-to)1058-1071
Number of pages14
JournalGenes and Development
Volume12
Issue number7
DOIs
StatePublished - Apr 1 1998
Externally publishedYes

Keywords

  • Apical ectodermal ridge
  • CD44
  • FGF
  • Limb development

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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