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induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells
1 Center for Immunology and Inflammatory Diseases, Division Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
2 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
3 Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
4 Department of Pathology, New England Regional Primate Research Center, Harvard Medical School, Southboro, MA 01772, USA
* These two authors contributed equally
Author for correspondence (e-mail: rklein{at}partners.org)
Accepted March 1, 2001
The chemokine SDF-1
(CXC12) and its receptor CXCR4 have been shown to play a role in the development of normal cerebellar cytoarchitecture. We report here that SDF-1 both induces chemotactic responses in granule precursor cells and enhances granule cell proliferative responses to Sonic hedgehog. Chemotactic and proliferative responses to SDF-1 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-1 activation of neuronal CXCR4 differs from activation of CXCR4 in leukocytes in that SDF-1-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-1 are all abolished by pretreatment of granule cells with pertussis toxin, suggesting they occur through Gi activation. In conclusion, SDF-1 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.
Key words: Chemokine, SDF-1, Sonic hedgehog, Granule cell, Cerebellum, Mouse
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