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

R. S. Klein, J. B. Rubin, H. Gibson, E. N. DeHaan, Alvarez-Hernandez, R. A. Segal, A. D. Luster

Research output: Contribution to journalArticlepeer-review

259 Scopus citations

Abstract

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 KC1 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.

Original languageEnglish
Pages (from-to)1971-1981
Number of pages11
JournalDevelopment
Volume128
Issue number11
StatePublished - 2001

Keywords

  • Cerebellum
  • Chemokine
  • Granule cell
  • Mouse
  • SDF-1α
  • Sonic hedgehog

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