FoxOs regulate multiple intracellular signaling pathways and are also required for long-term maintenance of adult neural precursors (Paik et al., 2009 and Renault et al., 2009). In contrast, Prox1 (Lavado et al., 2010), NeuroD (Gao et al., 2009 and Kuwabara et al., 2009), and Krüppel-like factor 9 (Scobie et al., 2009) are sequentially required for maturation and survival of new neurons in the adult hippocampus. In the adult SVZ, Olig2 specifies transient amplifying cell fate whereas Pax6 and Dlx-2 direct neuronal fate (Doetsch et al., 2002) and promote a dopaminergic periglomerular

phenotype in adult mice (Brill et al., 2008 and Hack et al., 2005). Various epigenetic mechanisms play important roles in fine tuning and coordinating gene expression during adult neurogenesis, including DNA methylation, histone modifications, and non-coding RNAs (reviewed by Sun et al., 2011). For example, Methyl-CpG-binding domain protein 1 (Mbd1) suppresses the expression of FGF-2 LDK378 solubility dmso and several miRNAs to control the balance between proliferation and differentiation during adult hippocampal neurogenesis (Liu et al., 2010). Among many histone modifiers, Mll1

(mixed-lineage leukemia 1), a TrxG member that encodes an H3K4 methyltransferase, is specifically required for neuronal differentiation in the adult SVZ, at least partially through its direct target Dlx2 (Lim et al., 2009). Bmi-1, a member of the PcG complex, is required for neural precursor maintenance in the adult SVZ through the cell-cycle inhibitor p16 (Molofsky et al., 2003). Through silencing Sox2 expression, HDAC2 is required for maturation selleck compound and survival of newborn neurons in the adult

brain, but not embryonic neurogenesis (Jawerka et al., 2010). In addition, several micoRNAs (miR124, 137, and 184) have been shown to fine tune the amount and timing of adult neurogenesis (reviewed by Sun et al., 2011). A number of neurological disease risk genes have been shown to regulate adult neurogenesis. In the adult SGZ, expression of human presenillin (PS) variants linked to early-onset familial Alzheimer’s disease in microglia impairs proliferation and neuronal fate commitment (Choi et al., 2008), whereas deletion of PS1 in forebrain excitatory neurons affects enrichment-induced hippocampal Mephenoxalone neurogenesis (Feng et al., 2001). PS1 mutants also exhibit impaired self-renewal and differentiation of adult SVZ precursors involving notch signaling (Veeraraghavalu et al., 2010). Deletion of doublecortin (DCX; a gene mutated in most cases of double cortex syndrome) in newborn neurons causes severe morphologic defects and delayed migration along the RMS (Koizumi et al., 2006). 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/GSK3β/β-catenin/neurogenin1 signaling cascade (Luo et al.