Fig. 6. Proposed model for SDF-1 effects on granule cell position and proliferation during cerebellar development. Depicted is a granule cell in the EGL of the neonatal cerebellum where its position enables it to respond to two separate factors: SHH and SDF-1. SHH, produced by Purkinje cells, is known to stimulate granule cell proliferation by releasing the inhibition of smoothened (SMO) that is exerted by the SHH receptor, patched (PTC). SHH effects can be blocked by PKA or forskolin. We propose that pial derived SDF-1, through the activation of G_i, reduces cAMP and PKA activity and thereby enhances SHH-induced proliferation. In addition, SDF-1 also promotes the localization of granule cells to the EGL through a chemotactic effect that is directed towards the pia. SDF-1 thus contributes to granule cell proliferation both directly, by augmenting SHH effects, and indirectly by maintaining granule cell position within the proliferative environment of the EGL. EGL, external granule cell layer; ML, molecular layer; IGL, internal granule cell layer; SDF-1, stromal derived factor-1;-SHH, Sonic hedgehog; PTC, patched; SMO, smoothened; PKA, protein kinase A.