Stox1 as a novel transcriptional suppressor of Math1 during cerebellar granule neurogenesis and medulloblastoma formation

Cerebellar granule neuronal progenitors (GNPs) are the precursors of cerebellar granule cells (CGCs) and are believed to be the cell of origin for medulloblastoma (MB), yet the molecular mechanisms governing GNP neurogenesis are poorly elucidated. Here, we demonstrate that storkhead box 1 (Stox1), a...

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Published inCell death and differentiation Vol. 23; no. 12; pp. 2042 - 2053
Main Authors Zhang, Chenlu, Ji, Zhongzhong, Wang, Minglei, Zhang, Weiwei, Yang, Rong, An, Huanping, Yang, Ru, van Abel, Daan, van Dijk, Marie, Yang, Xiaohang, Ou, Guangshuo, Zhu, Helen He, Gao, Wei-Qiang
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.12.2016
Nature Publishing Group
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Summary:Cerebellar granule neuronal progenitors (GNPs) are the precursors of cerebellar granule cells (CGCs) and are believed to be the cell of origin for medulloblastoma (MB), yet the molecular mechanisms governing GNP neurogenesis are poorly elucidated. Here, we demonstrate that storkhead box 1 (Stox1), a forkhead transcriptional factor, has a pivotal role in cerebellar granule neurogenesis and MB suppression. Expression of Stox1 is upregulated along with GNP differentiation and repressed by activation of sonic hedgehog (SHH) signaling. Stox1 exerts its neurogenic and oncosuppressing effect via direct transcriptional repression of Math1, a basic helix-loop-helix transcription activator essential for CGC genesis. This study illustrates a SHH-Stox1-Math1 regulatory axis in normal cerebellar development and MB formation.
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content type line 23
ISSN:1350-9047
1476-5403
DOI:10.1038/cdd.2016.85