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 language | English (US) |
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Pages (from-to) | 1058-1071 |
Number of pages | 14 |
Journal | Genes and Development |
Volume | 12 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 1998 |
Externally published | Yes |
Keywords
- Apical ectodermal ridge
- CD44
- FGF
- Limb development
ASJC Scopus subject areas
- Genetics
- Developmental Biology