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

• Published in: Cell 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
• Language: English
• Published: London Nature Publishing Group UK 01.12.2016; Nature Publishing Group
• Subjects: 13/31; 14/34; 14/63; 38/77; 631/378; 631/67/1922; Alzheimer's disease; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell cycle; Cell Cycle Analysis; Cell death; Genes; Life Sciences; Medical research; Neurogenesis; Original Paper; Stem Cells; Transcription factors; China
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2016.85

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.