Fig. 8. Model for oligodendrocyte progenitor proliferation. As the levels of soluble growth factors in vivo are both limiting and too low to induce OP proliferation by themselves, local co-signals are needed to keep OPs proliferative and unable to differentiate prematurely. So, for example, by contacting integrin αvβ3 ligands, such as Vn on adjacent cells (neurons and astrocytes), a proliferative OP response can be induced at physiological PDGF concentrations. Upon both integrin αvβ3 engagement and PDGFαR ligand binding, the PDGFαR is sequestered to discrete detergent-insoluble membrane signalling platforms. In these membrane compartments, the PDGFαR is able to (further) activate integrin αvβ3 via a PKC-dependent signalling pathway. As a consequence, OP proliferation is induced via an integrin αvβ3-mediated PI3K-pp70 S6K-dependent signalling pathway. The fact that OP proliferation is dependent on the simultaneous action of a local, short-range signal (integrin ligand) and a more general, long-range signal (soluble growth factor) makes it possible for OP proliferation to be tightly regulated.