title: Fibroblast growth factor receptor function is required for the orderly projection of ganglion cell axons in the developing mammalian retina.
abstract: During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.
authors.affiliation: Department of Experimental Pathology UMDS, Guy's Hospital, London, United Kingdom.
authors.forename: P A
authors.initials: PA
authors.lastname: Brittis
authors.forename: J
authors.initials: J
authors.lastname: Silver
authors.forename: F S
authors.initials: FS
authors.lastname: Walsh
authors.forename: P
authors.initials: P
authors.lastname: Doherty
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D016475:3T3 Cells; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D003512:Cyclohexanones / Q000494:pharmacology; D005136:Eye Proteins / Q000502:physiology*; D005326:Fetal Proteins / Q000502:physiology*; D008322:Mammals / Q000196:embryology; D051379:Mice; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D003512:Cyclohexanones; D005136:Eye Proteins; D005326:Fetal Proteins; D017468:Receptors, Fibroblast Growth Factor; C063302:KN 62; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine