Cooperation between sonic hedgehog and fibroblast growth factor/MAPK signalling pathways in neocortical precursors

Nicoletta Kessaris; Françoise Jamen; Lee L Rubin; William D Richardson

doi:10.1242/dev.01027

Cooperation between sonic hedgehog and fibroblast growth factor/MAPK signalling pathways in neocortical precursors

Development. 2004 Mar;131(6):1289-98. doi: 10.1242/dev.01027. Epub 2004 Feb 11.

Authors

Nicoletta Kessaris¹, Françoise Jamen, Lee L Rubin, William D Richardson

Affiliation

¹ Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London WC1E 6BT, UK.

PMID: 14960493
DOI: 10.1242/dev.01027

Abstract

Sonic hedgehog (SHH) and fibroblast growth factor 2 (FGF2) can both induce neocortical precursors to express the transcription factor OLIG2 and generate oligodendrocyte progenitors (OLPs) in culture. The activity of FGF2 is unaffected by cyclopamine, which blocks Hedgehog signalling, demonstrating that the FGF pathway to OLP production is Hedgehog independent. Unexpectedly, SHH-mediated OLP induction is blocked by PD173074, a selective inhibitor of FGF receptor (FGFR) tyrosine kinase. SHH activity also depends on mitogen-activated protein kinase (MAPK) but SHH does not itself activate MAPK. Instead, constitutive activity of FGFR maintains a basal level of phosphorylated MAPK that is absolutely required for the OLIG2- and OLP-inducing activities of SHH. Stimulating the MAPK pathway with a retrovirus encoding constitutively active RAS shows that the requirement for MAPK is cell-autonomous, i.e. MAPK is needed together with SHH signalling in the cells that become OLPs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Basic Helix-Loop-Helix Transcription Factors
Fibroblast Growth Factor 2 / metabolism
Fibroblast Growth Factors / metabolism*
Hedgehog Proteins
Mice
Mitogen-Activated Protein Kinases / metabolism*
Neocortex / embryology*
Neocortex / metabolism
Nerve Tissue Proteins / metabolism
Oligodendrocyte Transcription Factor 2
Oligodendroglia / metabolism
Receptor Protein-Tyrosine Kinases / metabolism
Receptor, Fibroblast Growth Factor, Type 1
Receptors, Fibroblast Growth Factor / metabolism
Signal Transduction / physiology*
Trans-Activators / metabolism*

Substances

Basic Helix-Loop-Helix Transcription Factors
Hedgehog Proteins
Nerve Tissue Proteins
Olig2 protein, mouse
Oligodendrocyte Transcription Factor 2
Receptors, Fibroblast Growth Factor
Shh protein, mouse
Trans-Activators
Fibroblast Growth Factor 2
Fibroblast Growth Factors
Fgfr1 protein, mouse
Receptor Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 1
Mitogen-Activated Protein Kinases