Previous biochemical analysis and yeast two-hybrid screen have identified a large number of DISC1-interacting proteins, named “DISC1 interactome” (Camargo et al., 2007). The functional significance of these potential interactions is largely unexplored. Our current study provided novel insight into the function of KIAA1212 as a critical mediator, through which DISC1 modulates AKT signaling in neuronal development. The time course of KIAA1212 expression during differentiation of adult neural progenitor (Figure S2) correlates with the gradually elevated AKT signaling in newborn neurons with DISC1 knockdown in vivo (Figure 1). The lack of KIAA1212 expression in adult neural progenitors raises an intriguing possibility of developmental stage-dependent regulation by DISC1 during adult neurogenesis. In support of this notion, DISC1 was shown to regulate proliferation of adult neural progenitors through inhibition of GSK3β, a downstream target of AKT (Mao et al., 2009), whereas our genetic and pharmacological studies demonstrated a role of DISC1 in regulating development of post-mitotic newborn neurons through mTOR (Figure 7). Whether GSK3β plays a cell autonomous role in regulating development of newborn neurons in the adult brain remains to be fully
