Stox1 as a novel transcriptional suppressor of Math1 during cerebellar granule neurogenesis and medulloblastoma formation.
Chenlu ZhangZhongzhong JiMinglei WangWeiwei ZhangRong YangHuanping AnRu YangDaan van AbelMarie van DijkXiaohang YangGuangshuo OuHelen He ZhuWei-Qiang GaoPublished in: Cell death and differentiation (2016)
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.
Keyphrases
- transcription factor
- dna binding
- gene expression
- cerebral ischemia
- induced apoptosis
- single cell
- poor prognosis
- heat shock
- cell therapy
- mesenchymal stem cells
- signaling pathway
- oxidative stress
- endoplasmic reticulum stress
- cell proliferation
- inflammatory response
- blood brain barrier
- cell cycle arrest
- long non coding rna
- heat shock protein