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The Journal of Neuroscience, June 1, 2003, 23(11):4601-4612

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The Chemokine Stromal Cell-Derived Factor-1 Promotes the Survival of Embryonic Retinal Ganglion Cells

Sreekanth H. Chalasani,1 Frédéric Baribaud,2 Christine M. Coughlan,2 Mary J. Sunshine,4 Virginia M. Y. Lee,3 Robert W. Doms,2 Dan R. Littman,4 and Jonathan A. Raper1

1 Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, 2 Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, 3 Department of Pathology and Laboratory Medicine and Center for Neurodegenerative Diseases Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and 4 Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016

The chemokine receptor CXCR4 is expressed in the embryonic and mature CNS, yet its normal physiological function in neurons remains obscure. Here, we show that its cognate chemokine, stromal cell-derived factor-1 (SDF-1), promotes the survival of cultured embryonic retinal ganglion cell neurons even in the absence of other neurotrophic factors. This survival effect is mediated primarily through a cAMP-dependent pathway that acts through protein kinase A and MAP kinase. Addition of SDF-1 to a human neuronal cell line induces phosphorylation of p44/p42 MAP kinase and GSK3{beta}. Mouse embryos lacking the CXCR4 receptor have a reduced number of retinal ganglion cells. The ligand of CXCR4, SDF-1, may therefore provide generalized trophic support to neurons during their development and maturation.

Key words: SDF-1; slit-2; RGC; cAMP; survival; neurotrophic

Received Aug. 30, 2002; revised Mar. 7, 2003; accepted Mar. 17, 2003.




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