SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells

The chemokine SDF-1 alpha (CXC12) and its receptor CXCR4 have been shown to play a role in the development of normal cerebellar cytoarchitecture. We r eport here that SDF-1 alpha both induces chemotactic responses in granule p recursor cells and enhances granule cell proliferative responses to Sonic h edgehog. Chemotactic and proliferative responses to SDF-1 alpha are greater in granule cells obtained from cerebella of animals in the first postnatal week, coinciding with the observed in vivo peak in cerebellar CXCR4 expres sion. SDF-1 alpha activation of neuronal CXCR4 differs from activation of C XCR4 in leukocytes in that SDF-1 alpha -induced calcium flux is activity de pendent, requiring predepolarization with KCI or pretreatment with glutamat e. However, as is the case in leukocytes, neuronal responses to SDF-1 alpha are all abolished by pretreatment of granule cells with pertussis toxin, s uggesting they occur through G(alphai) activation. In conclusion, SDF-1 alp ha plays a role in two important processes of granule cell maturation - pro liferation and migration assisting in the achievement of appropriate cell n umber and position in the cerebellar cortex.