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Updated: Aug 17, 2026

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Multiple signaling pathways regulate FGF-2-induced retinal ganglion cell neurite extension and growth cone guidance

C A Webber1, Y Y Chen, C L Hehr

  • 1Genes and Development Research Group, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB, Canada T2N 4N1.

Molecular and Cellular Neurosciences
|July 6, 2005
PubMed

Insights

Fibroblast growth factors (FGFs) guide retinal ganglion cell (RGC) axons. FGF-2 stimulates RGC neurite extension via MAPK and PLC pathways, but directional growth relies solely on PLC signaling.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Axon guidance is crucial for neural circuit formation.
  • Fibroblast growth factors (FGFs) are key signaling molecules in axon guidance.
  • Intracellular pathways like MAPK, PI3K, and PLC mediate FGF receptor signaling.

Purpose of the Study:

  • To identify the specific intracellular signaling pathways mediating FGF-2-induced retinal ganglion cell (RGC) axon extension and chemorepulsion in Xenopus laevis.
  • To differentiate the roles of MAPK, PI3K, and PLC pathways in neurite outgrowth versus directed growth.

Main Methods:

  • Pharmacological inhibition of MAPK (U0126), PI3K (LY249002), and PLCgamma (U73122) pathways.
  • Assessment of FGF-2's effects on RGC neurite extension in vitro.
  • Testing the role of the phosphotidylcholine-PLC (PC-PLC) pathway using D609.

Main Results:

  • FGF-2-stimulated RGC neurite extension in vitro requires both MAPK and two PLC pathways.
  • Axon response to asymmetric FGF-2 application, indicative of chemorepulsion, depends exclusively on PLC pathways.
  • PI3K pathway does not appear to be essential for FGF-2-mediated axon extension or guidance.

Conclusions:

  • Both MAPK and PLC signaling cascades are necessary for FGF-2 to promote general RGC axon extension.
  • PLC pathways are critically involved in the directional guidance of RGC axons in response to FGF-2.
  • This study elucidates the distinct roles of intracellular signaling in axon growth versus guidance, highlighting the specificity of PLC in directed neurite navigation.

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