Multiple signaling pathways regulate FGF-2-induced retinal ganglion cell neurite extension and growth cone guidance

Mol Cell Neurosci. 2005 Sep;30(1):37-47. doi: 10.1016/j.mcn.2005.05.005.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / physiology*
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology*
  • Growth Cones / drug effects
  • Growth Cones / physiology*
  • Humans
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phospholipase C gamma
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / ultrastructure*
  • Type C Phospholipases / metabolism
  • Xenopus laevis

Substances

  • Fibroblast Growth Factor 2
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • Phospholipase C gamma