Examining the Functional Role of Fragile X Related Protein 1(FXR1P) in Adult Neurogenesis

FXR1P is a member of the fragile X family of RNA binding proteins, which includes FMRP and FXR2P. Both FMRP and FXR2P regulate adult neural stem cells (aNSCs) and neurogenesis, a process affected in a number of neurological and neuropsychiatric disorders, including Fragile X syndrome. Although FXR1P has been implicated in diverse developmental processes and neuropsychiatric diseases, its role in neurodevelopment is not well understood. The goal of this study is to elucidate the function of FXR1P in adult neurogenesis. We used an inducible triple transgenic mouse model ( Fxr1 ‐cKO; Nestin ‐ CreER T2 ; Ai14 ::tdTomato) that allows us to investigate how FXR1P deficiency in aNSCs affects proliferation and fate specification. Deletion of FXR1 in aNSCs resulted in fewer adult‐born cells and reduced populations of radial glia‐like cells, neuroblasts, immature neurons, neurons, and astrocytes. We hypothesize that this reduction in new cell numbers resulted from impaired proliferation, which we confirmed in vitro using primary aNSCs. In addition, we found that mRNAs related to cell cycle progression were downregulated in vitro . Ongoing work includes identification of mRNAs regulated by FXR1P in aNSCs. These results indicate that FXR1P plays an important role in regulating aNSC self‐renewal and maintenance in the adult brain. Support or Funding Information NIH (MH080434, MH07897) to X.Z.; Waisman Center core grant NIH(P30HD03352); Molecular and Cellular Pharmacology Training Grant NIH(T32 GM008688) to N.E.P.; a NIMH‐NIH NSRA (F31MH103945) to N.E.P.; the Wayne and Jean Roper Memorial Wisconsin Distinguished Graduate Student Fellowship to N.E.P and the Hilldale Undergraduate Fellowship to KN.