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 report here that SDF-1 alpha both induces chemotactic responses in granule precursor cells and enhances granule cell proliferative responses to Sonic hedgehog. 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 expression. SDF-1 alpha activation of neuronal CXCR4 differs from activation of CXCR4 in leukocytes in that SDF-1 alpha-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 alpha are all abolished by pretreatment of granule cells with pertussis toxin, suggesting they occur through G(alpha i) activation. In conclusion, SDF-1 alpha 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.
Klein
R S
RS
Center for Immunology and Inflammatory Diseases, Division Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. rklein@partners.org
Rubin
J B
JB
Gibson
H D
HD
DeHaan
E N
EN
Alvarez-Hernandez
X
X
Segal
R A
RA
Luster
A D
AD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D016764:Cell Polarity; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D005260:Female; D053823:Hedgehog Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D053823:Hedgehog Proteins; D019718:Receptors, CXCR4; D015534:Trans-Activators; D002118:Calcium