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

First Author  Luo Y Year  2010
Journal  PLoS Genet Volume  6
Issue  4 Pages  e1000898
PubMed ID  20386739 Mgi Jnum  J:159211
Mgi Id  MGI:4442089 Doi  10.1371/journal.pgen.1000898
Citation  Luo Y, et al. (2010) Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells. PLoS Genet 6(4):e1000898
abstractText  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.
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