Neural precursor cycling at sonic speed: N-Myc pedals, GSK-3 brakes

Paul S Knoepfler, Anna Marie Kenney

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Signaling by the sonic hedgehog (Shh) pathway is essential for neural precursor population expansion during normal central nervous system (CNS) development, and is implicated in the childhood brain tumor, medulloblastoma. the proto-oncogene N-myc plays essential roles as a downstream effector of Shh proliferative effects in neural precursors of the cerebellum, where medulloblastomas arise. It is likely that N-Myc has analogous functions in medulloblastomas and other CNS tumors where it is highly expressed due to altered regulation or gene amplification. Myc destabilization occurs in response to phosphorylation by GSK-3β. N-Myc degradation is required for cerebellar neural precursors to exit the cell cycle. During mitosis in cerebellar neural precursors, levels of N-Myc primed for phosphorylation by GSK-3βincrease, due to cdk1 complex activity towards N-Myc. GSK-3β is kept in check by insulin-like growth factor signaling, which also plays critical roles in brain development and cancer. These findings indicate that therapeutic strategies targeting N-myc and the IGF pathway might be effective against medulloblastoma.

Original languageEnglish (US)
Pages (from-to)47-52
Number of pages6
JournalCell Cycle
Volume5
Issue number1
StatePublished - Jan 1 2006
Externally publishedYes

Keywords

  • Cell cycle
  • Cerebellum
  • Insulin-like growth factor
  • Medulloblastoma
  • N-myc
  • Progenitor cells
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

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