title: The chemokine stromal cell-derived factor-1 promotes the survival of embryonic retinal ganglion cells.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Sreekanth H
authors.initials: SH
authors.lastname: Chalasani
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baribaud
authors.forename: Christine M
authors.initials: CM
authors.lastname: Coughlan
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Sunshine
authors.forename: Virginia M Y
authors.initials: VM
authors.lastname: Lee
authors.forename: Robert W
authors.initials: RW
authors.lastname: Doms
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Raper
mesh_terms: 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
chemical_list: 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