Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development

Haotian Zhao, Olivier Ayrault, Frederique Zindy, Jee Hae Kim, Martine F. Roussel

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Bone morphogenic proteins 2 and 4 (BMP2 and BMP4) inhibit proliferation and induce differentiation of cerebellar granule neuron progenitors (GNPs) and primary GNP-like medulloblastoma (MB) cells. This occurs through rapid proteasome-mediated degradation of Math1 (Atoh1), a transcription factor expressed in proliferating GNPs. Ectopic expression of Atoh1, but not of Sonic hedgehog (Shh)-regulated Gli1 or Mycn, cancels these BMP-mediated effects and restores Shh-dependent proliferation of GNPs and MB cells in vitro and in vivo. Genes regulating the BMP signaling pathway are down-regulated in mouse MBs. Thus, BMPs are potent inhibitors of MB and should be considered as novel therapeutic agents.

Original languageEnglish (US)
Pages (from-to)722-727
Number of pages6
JournalGenes and Development
Volume22
Issue number6
DOIs
StatePublished - Mar 15 2008

Keywords

  • Atoh1/Math1
  • Bone morphogenic protein
  • Medulloblastoma
  • Mycn
  • Sonic hedgehog

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development'. Together they form a unique fingerprint.

  • Cite this