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Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.

Yuping Luo | Ge Shan | Weixiang Guo | Richard D Smrt | Eric B Johnson | Xuekun Li | Rebecca L Pfeiffer | Keith E Szulwach | Ranhui Duan | Basam Z Barkho | Wendi Li | Changmei Liu | Peng Jin | Xinyu Zhao
PLoS genetics | 2010

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

Pubmed ID: 20386739

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Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R56 MH076090
  • Agency: NIGMS NIH HHS, United States
    Id: 2R25GM060201-09
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH080434
  • Agency: NINDS NIH HHS, United States
    Id: NS051630
  • Agency: NIGMS NIH HHS, United States
    Id: R25 GM060201
  • Agency: NIMH NIH HHS, United States
    Id: MH078972
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS051630
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH078972
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH076090
  • Agency: NIMH NIH HHS, United States
    Id: MH080434
  • Agency: NIMH NIH HHS, United States
    Id: MH076090

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HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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