Multiple signaling pathways regulate FGF-2-induced retinal ganglion cell neurite extension and growth cone guidance.
Growth cones use cues in their environment in order to grow in a directed fashion to their targets. In Xenopus laevis, fibroblast growth factors (FGFs) participate in retinal ganglion cell (RGC) axon guidance in vivo and in vitro. The main intracellular signaling cascades known to act downstream of the FGF receptor include the mitogen-activated protein kinase (MAPK), phospholipase Cgamma (PLCgamma) and phosphotidylinositol 3-kinase (PI3K) pathways. We used pharmacological inhibitors to identify the signaling cascade(s) responsible for FGF-2-stimulated RGC axon extension and chemorepulsion. The MAPK, PI3K and PLCgamma pathways were blocked by U0126, LY249002 and U73122, respectively. D609 was used to test a role for the phosphotidylcholine-PLC (PC-PLC) pathway. We determined that the MAPK and two PLC pathways are required for FGF-2 to stimulate RGC neurite extension in vitro, but the response of axons to FGF-2 applied asymmetrically to the growth cone depended only on the PLC pathways.
Genes and Development Research Group, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB, Canada T2N 4N1.
C A
CA
Webber
Y Y
YY
Chen
C L
CL
Hehr
J
J
Johnston
S
S
McFarlane
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000648:ultrastructure*; D010738:Type C Phospholipases / Q000378:metabolism; D014982:Xenopus laevis
D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma