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

By Yuping Luo, G. Shan, Weixiang Guo, Richard D. Smrt, Eric B. Johnson, Xuekun Li, Rebecca L. Pfeiffer, Keith E. Szulwach, R. Duan, B. Barkho and 4 more. 2010

235 citations recorded by the source corpus.

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 GSK3β. Dysregulation of GSK3β 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.

Subfields: Genetics, Molecular Biology

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The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Guo-li Ming
2. Hongjun Song
3. German Ignacio Parisi
4. Fred H. Gage

In Molecular Biology

1. Hongjun Song
2. Guo-li Ming
3. Pierre Marie Lledo
4. C. Greer
5. Fred H. Gage
6. German Ignacio Parisi

Citations in the corpus

• Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “In mice deficient in fragile X mental retardation protein (Fmrp; a gene responsible for fragile X syndrome), both proliferation and glial fate commitment of neural precursors are increased in the adult SGZ, through regulation of the Wnt/GSK3b/b-catenin/neurogenin1 signaling cascade (Luo et al., 2010”
• Fragile X Mental Retardation Protein Regulates New Neuron Differentiation in the Adult Olfactory Bulb (2011, background): “Because Fmrp has recently been involved in regulating neural stem cells proliferation (Callan et al., 2010; Luo et al., 2010), we first tested whether the production and early maturation of young 8 dpi GCs was not altered after induction of Fmr1 mutation in the SVZ (supplemental Fig.”