Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/progenitor Cells

Overview

Journal PLoS Genet

Specialty Genetics

Date 2010 Apr 14

PMID 20386739

Citations 147

Authors

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

Affiliations

Soon will be listed here.

Abstract

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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