The chemokine SDF-1α (CXC12) and its receptor CXCR4 have been shown to play a role in the development of normal cerebellar cytoarchitecture. We report here that SDF-1α both induces chemotactic responses in granule precursor cells and enhances granule cell proliferative responses to Sonic hedgehog. Chemotactic and proliferative responses to SDF-1α 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 expression. SDF-1α activation of neuronal CXCR4 differs from activation of CXCR4 in leukocytes in that SDF-1α-induced calcium flux is activity dependent, requiring predepolarization with KCl or pretreatment with glutamate. However, as is the case in leukocytes, neuronal responses to SDF-1α are all abolished by pretreatment of granule cells with pertussis toxin, suggesting they occur through Gαi activation. In conclusion, SDF-1α plays a role in two important processes of granule cell maturation – proliferation and migration – assisting in the achievement of appropriate cell number and position in the cerebellar cortex.
SDF-1α induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells
Robyn S. Klein, Joshua B. Rubin, Hilary D. Gibson, Elliot N. DeHaan, Xavier Alvarez-Hernandez, Rosalind A. Segal, Andrew D. Luster; SDF-1α induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development 1 June 2001; 128 (11): 1971–1981. doi: https://doi.org/10.1242/dev.128.11.1971
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