在小脑颗粒神经发生和髓母细胞瘤形成过程中，Stox1作为Math1的一种新型转录抑制因子。
Stox1 as a novel transcriptional suppressor of Math1 during cerebellar granule neurogenesis and medulloblastoma formation.
作者信息
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
机构信息
State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
出版信息
Cell Death Differ. 2016 Dec;23(12):2042-2053. doi: 10.1038/cdd.2016.85. Epub 2016 Aug 26.
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.
摘要
小脑颗粒神经元祖细胞（GNPs）是小脑颗粒细胞（CGCs）的前体，被认为是髓母细胞瘤（MB）的起源细胞，但调控GNP神经发生的分子机制仍不清楚。在此，我们证明了叉头转录因子鹳头盒1（Stox1）在小脑颗粒神经发生和MB抑制中起关键作用。Stox1的表达随着GNP分化而上调，并被音猬因子（SHH）信号通路的激活所抑制。Stox1通过直接转录抑制Math1发挥其神经发生和肿瘤抑制作用，Math1是CGC发生所必需的一种基本螺旋-环-螺旋转录激活因子。本研究阐明了正常小脑发育和MB形成中的SHH-Stox1-Math1调控轴。
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