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Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells.

Publication ,  Journal Article
Fogarty, MP; Emmenegger, BA; Grasfeder, LL; Oliver, TG; Wechsler-Reya, RJ
Published in: Proc Natl Acad Sci U S A
February 20, 2007

The Sonic hedgehog (Shh) and FGF signaling pathways regulate growth and differentiation in many regions of the nervous system, but interactions between these pathways have not been studied extensively. Here, we examine the relationship between Shh and FGF signaling in granule cell precursors (GCPs), which are the most abundant neural progenitors in the cerebellum and the putative cell of origin for the childhood brain tumor medulloblastoma. In these cells, Shh induces a potent proliferative response that is abolished by coincubation with basic FGF. FGF also inhibits transcription of Shh target genes and prevents activation of a Gli-responsive promoter in fibroblasts, which suggests that it blocks Shh signaling upstream of Gli-mediated transcription. FGF-mediated inhibition of Shh responses requires activation of FGF receptors and of ERK and JNK kinases, because it can be blocked by inhibitors of these enzymes. Finally, FGF promotes differentiation of GCPs in vitro and in vivo and halts proliferation of tumor cells from patched (ptc) mutant mice, a model for medulloblastoma. These findings suggest that FGF is a potent inhibitor of Shh signaling and may be a useful therapy for tumors involving activation of the hedgehog pathway.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 20, 2007

Volume

104

Issue

8

Start / End Page

2973 / 2978

Location

United States

Related Subject Headings

  • Stem Cells
  • Signal Transduction
  • Receptors, Fibroblast Growth Factor
  • Receptors, Cell Surface
  • Patched-1 Receptor
  • Patched Receptors
  • Neurons
  • Neoplasms
  • Mutant Proteins
  • Mitogen-Activated Protein Kinases
 

Citation

APA
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ICMJE
MLA
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Fogarty, M. P., Emmenegger, B. A., Grasfeder, L. L., Oliver, T. G., & Wechsler-Reya, R. J. (2007). Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells. Proc Natl Acad Sci U S A, 104(8), 2973–2978. https://doi.org/10.1073/pnas.0605770104
Fogarty, Marie P., Brian A. Emmenegger, Linda L. Grasfeder, Trudy G. Oliver, and Robert J. Wechsler-Reya. “Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells.Proc Natl Acad Sci U S A 104, no. 8 (February 20, 2007): 2973–78. https://doi.org/10.1073/pnas.0605770104.
Fogarty MP, Emmenegger BA, Grasfeder LL, Oliver TG, Wechsler-Reya RJ. Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2973–8.
Fogarty, Marie P., et al. “Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells.Proc Natl Acad Sci U S A, vol. 104, no. 8, Feb. 2007, pp. 2973–78. Pubmed, doi:10.1073/pnas.0605770104.
Fogarty MP, Emmenegger BA, Grasfeder LL, Oliver TG, Wechsler-Reya RJ. Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2973–2978.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 20, 2007

Volume

104

Issue

8

Start / End Page

2973 / 2978

Location

United States

Related Subject Headings

  • Stem Cells
  • Signal Transduction
  • Receptors, Fibroblast Growth Factor
  • Receptors, Cell Surface
  • Patched-1 Receptor
  • Patched Receptors
  • Neurons
  • Neoplasms
  • Mutant Proteins
  • Mitogen-Activated Protein Kinases