of truncated forms (Hikida et al., 2007; Li et al., 2007; Pletnikov et al., 2008; Shen et al., 2008), deletion of certain isoforms (Ishizuka et al., 2007; Koike et al., 2006; Kvajo et al., 2008) and lentivirus-mediated expression of short-hairpin RNA (shRNA) against disc1 in the adult dentate gyrus (Mao et al., 2009). In vitro studies with PC12 cells and primary neurons showed that blocking DISC1 function impairs neurite outgrowth (Kamiya et al., 2006; Ozeki et al., 2003; Taya et al., 2007). In utero electroporation-mediated knockdown of DISC1, or expression of a truncated form of DISC1, in E14.5 embryos leads to retarded migration and mis-oriented dendrites of cortical neurons (Kamiya et al., 2005), whereas electroporation of shRNAs against disc1 in E13 embryos leads to premature cell cycle exit and neuronal differentiation (Mao et al., 2009). In contrast, retrovirus-mediated knockdown of DISC1 by shRNAs specifically in proliferating neural progenitors in the adult hippocampus leads to soma hypertrophy, ectopic dendrites and increased tempo of development of newborn dentate granule cells, including over-extended migration, accelerated axon and dendrite development as well as synapse formation (Duan et al., 2007; Faulkner et al., 2008). The signaling mechanisms by which DISC1 regulates different aspects of neuronal
