Emerging evidence support the notion that DISC1 functions as a key regulator for a number of developmental processes in the nervous system (Ishizuka et al., 2006; Mackie et al., 2007). During adult neurogenesis, DISC1 controls the tempo of cell cycle exit of neural progenitors and multiple processes of neuronal development of newborn neurons (Ming and Song, 2009). In this study, we identified AKT-mTOR signaling as a previously unexpected target of DISC1 in regulation of morphogenesis and dendritic development of new neurons in the adult brain (Figure 7). We further pinpointed KIAA1212, a protein binding to DISC1 and AKT, as the critical mediator in linking these two molecules into the same signaling pathway. Our results suggest that DISC1 modulates AKT signaling in newborn neurons through its interaction with KIAA1212 (Figure 7). This model, based on in vitro biochemical analysis of protein-protein interaction and its effect on AKT signaling, is supported by histological evidence of over-activation of AKT signaling in newborn neurons with DISC1 suppression, and by in vivo findings that multiple approaches to over-activate AKT signaling all lead to phenotypes similar
