The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of αvβ3 integrins

Wia Baron, Sanford J. Shattil, Charles Ffrench-Constant

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121 Citations (Scopus)


Central nervous system development requires precise and localized regulation of neural precursor behaviour. Here we show how the interaction between growth factor and integrin signalling pathways provides a mechanism for such precision in oligodendrocyte progenitor (OP) proliferation. While physiological concentrations of platelet-derived growth factor (PDGF) were not in themselves sufficient to promote OP proliferation, they did so on extracellular matrix (ECM) substrate that bind αvβ3 integrin. Upon PDGF-AA exposure and αvβ3 engagement, a physical co-association between both receptors was demonstrated, confirming the interaction between these signalling pathways. Furthermore, we found that PDGFaR stimulated a protein kinase C-dependent activation of integrin αvβ3, which in turn induced OP proliferation via a phosphatidylinositol 3-kinase-dependent signalling pathway. These studies establish a mechanism by which OP proliferation is dependent on the availability of both an ECM ligand and a mitogenic growth factor. Growth factor-mediated integrin activation is the critical integrative step in proliferation signalling, and ensures that the response of neural precursor cells to long-range cues can be regulated by their cellular neighbours, allowing precise control of cell behaviour during development.

Original languageEnglish
Pages (from-to)1957-1966
Number of pages10
JournalEMBO Journal
Issue number8
Publication statusPublished - 15 Apr 2002


  • Activation
  • Extracellular matrix
  • Integrin
  • PDGF
  • WOW-1

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