Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells

Zeng Jie Yang, Tammy Ellis, Shirley L. Markant, Tracy Ann Read, Jessica D. Kessler, Melissa Bourboulas, Ulrich Schüller, Robert Machold, Gord Fishell, David H. Rowitch, Brandon J. Wainwright, Robert J. Wechsler-Reya

Research output: Contribution to journalArticlepeer-review

534 Scopus citations


Medulloblastoma is the most common malignant brain tumor in children, but the cells from which it arises remain unclear. Here we examine the origin of medulloblastoma resulting from mutations in the Sonic hedgehog (Shh) pathway. We show that activation of Shh signaling in neuronal progenitors causes medulloblastoma by 3 months of age. Shh pathway activation in stem cells promotes stem cell proliferation but only causes tumors after commitment to-and expansion of-the neuronal lineage. Notably, tumors initiated in stem cells develop more rapidly than those initiated in progenitors, with all animals succumbing by 3-4 weeks. These studies suggest that medulloblastoma can be initiated in progenitors or stem cells but that Shh-induced tumorigenesis is associated with neuronal lineage commitment.

Original languageEnglish (US)
Pages (from-to)135-145
Number of pages11
JournalCancer Cell
Issue number2
StatePublished - Aug 12 2008
Externally publishedYes



ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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