The chemokine stromal cell-derived factor-1 promotes the survival of embryonic retinal ganglion cells.
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 GSK3beta. 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.
Chalasani
Sreekanth H
SH
Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Baribaud
Frédéric
F
Coughlan
Christine M
CM
Sunshine
Mary J
MJ
Lee
Virginia M Y
VM
Doms
Robert W
RW
Littman
Dan R
DR
Raper
Jonathan A
JA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D018925:Chemokines / Q000494:pharmacology*; D019743:Chemokines, CXC / Q000494:pharmacology*; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction / Q000502:physiology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D009414:Nerve Growth Factors; D019718:Receptors, CXCR4; D000242:Cyclic AMP; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3