title: Stox1 as a novel transcriptional suppressor of Math1 during cerebellar granule neurogenesis and medulloblastoma formation.
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.
authors: 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.
authors: Chenlu
authors: C
authors: Zhang
authors: 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.
authors: Zhongzhong
authors: 0000-0003-0562-2477
authors: Z
authors: Ji
authors: 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.
authors: Minglei
authors: M
authors: Wang
authors: 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.
authors: Weiwei
authors: W
authors: Zhang
authors: School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
authors: Rong
authors: R
authors: Yang
authors: College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Huanping
authors: H
authors: An
authors: 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.
authors: Ru
authors: R
authors: Yang
authors: Department of Clinical Chemistry, VU University Medical Center, de Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.
authors: Daan
authors: D
authors: van Abel
authors: Department of Clinical Chemistry, VU University Medical Center, de Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.
authors: Marie
authors: M
authors: van Dijk
authors: College of Life Sciences, Zhejiang University, Hangzhou 310058, China.|Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors: Xiaohang
authors: X
authors: Yang
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Guangshuo
authors: G
authors: Ou
authors: 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.
authors: Helen He
authors: HH
authors: Zhu
authors: 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.|Collarative Innovation Center of Systems Biomedicine, Shanghai, China.
authors: Wei-Qiang
authors: WQ
authors: Gao
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D000072079:Patched Receptors / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D053823:Hedgehog Proteins; D000072079:Patched Receptors; C500943:Atoh1 protein, mouse; C000596379:STOX1 protein, mouse; C465570:Shh protein, mouse