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

Chenlu Zhang, Zhongzhong Ji, Minglei Wang, Weiwei Zhang, Rong Yang, Huanping An, Ru Yang, Daan van Abel, Marie van Dijk, Xiaohang Yang, Guangshuo Ou, Helen He Zhu, Wei-Qiang Gao

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)2042-2053
JournalCell Death and Differentiation
Volume23
Issue number12
DOIs
Publication statusPublished - Dec 2016

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