Second, our study demonstrates that a single molecular player has a dramatically different effect on development during early postnatal and adult neurogenesis. Previous studies have largely found conserved roles of extrinsic morphogens, growth factors and neurotransmitters, and intrinsic transcriptional factors and cytoplasmic signaling molecules (Ming and Song, 2011). Here we show that DISC1 keeps the tempo of neuronal maturation in check during adult neurogenesis to prevent runaway signaling from a positive feed-back loop that functions to promote dendritic growth of new neurons: increased depolarizing GABAergic signaling leads to increased dendritic growth and potentially more GABAergic inputs, which in turn drive more dendritic growth. This gating role of DISC1 is diminished during early postnatal neurogenesis when GABA-induced depolarization is transient (Figure 5F). These results support the notion that DISC1 serves as an important determinant, instead of direct mediator, of extrinsic stimulation in regulating neuronal development. Our findings provide novel molecular insights into the differential regulation of early postnatal and adult neurogenesis and indicate that adult neurogenesis is not simply a continuation of ongoing neuronal development into adulthood.
