title: A splice variant of CD44 expressed in the apical ectodermal ridge presents fibroblast growth factors to limb mesenchyme and is required for limb outgrowth.
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.
authors.affiliation: Forschungszentrum Karlsruhe, Institut für Genetik, D-76021 Karlsruhe, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Sherman
authors.forename: D
authors.initials: D
authors.lastname: Wainwright
authors.forename: H
authors.initials: H
authors.lastname: Ponta
authors.forename: P
authors.initials: P
authors.lastname: Herrlich
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005121:Extremities / Q000196:embryology; D051519:Fibroblast Growth Factor 4; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000276:immunology / Q000378:metabolism*; D006133:Growth Substances / Q000276:immunology / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D051381:Rats
chemical_list: C496447:Fgf4 protein, rat; C496458:Fgf8 protein, rat; D051519:Fibroblast Growth Factor 4; D006133:Growth Substances; D018960:Hyaluronan Receptors; D011518:Proto-Oncogene Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors