In a similar situation, we previously showed that FMRP deficiency in mice leads to impaired hippocampal neurogenesis and hippocampal-dependent learning and that FMRP regulates DG-NPCs via
check details the Wnt signaling pathway ( Guo et al., 2011 and Luo et al., 2010). However, in the current study, we discovered that DG-NPCs in Fxr2 KO mice have increased neuronal differentiation with no change in Wnt signaling in Fxr2 KO DG-NPCs. In addition, FMRP inhibits Gsk3β protein expression by repressing translation without affecting Gsk3β mRNA stability, whereas FXR2 represses Noggin protein expression by reducing the stability of Noggin mRNA. Furthermore, FMRP deficiency results in increased proliferation of both stem cells and transient amplifying cells in the adult DG ( Luo et al., 2010), and loss of FXR2 only affects stem cell proliferation in the DG. Therefore, both FMRP and FXR2 can regulate adult hippocampal NPCs by binding to the mRNAs of NPC regulators, but their mechanisms, as
well as their functional outputs, are different. Posttranscriptional regulation of critical regulatory mRNAs by RNA-binding proteins is likely to be a common mechanism during critical cellular processes ( Bhattacharyya see more et al., 2008, Callan et al., 2010, Tervonen et al., 2009 and Yang et al., 2009), but evidence for this in adult mammalian neurogenesis is rather limited. Our data are among the first to demonstrate that RNA-binding proteins can play important roles in the differential regulation of NPCs residing in different adult brain regions. Future studies examining the role of FXR2 in generating the inhibitory interneurons of the olfactory bulb and excitatory neurons of the DG, particularly in comparison with FMRP, will further contribute to our knowledge of these important RNA-binding proteins in adult neurogenesis and plasticity. All animal procedures were performed according to protocols approved by the University of
New Mexico Animal Care and Use Committee. The Fxr2 KO mouse strain on the C57B/L6 genetic background published previously ( Bontekoe et al., 2002) was obtained from the Emory University fragile X consortium. The NogginLacZ all transgenic mice were maintained and genotyped as described previously ( Stottmann et al., 2001). In vivo neurogenesis analyses were performed essentially as we have previously described (Guo et al., 2011, Luo et al., 2010, Smrt et al., 2007 and Zhao et al., 2003). Mice were given four injections of BrdU (50 mg/kg) within 12 hr to label all dividing cells in adult germinal zones within this time period based on a published paradigm (Hayes and Nowakowski, 2002). Mice were then euthanized either at either 12 hr or one week following the final BrdU injection. Antibody information is provided in Supplemental Experimental Procedures. Quantification of BrdU+ cells in the DG and SVZ and phenotypic analysis of BrdU+ cells were performed as described previously.