We next examined dendritic development of new neurons by reconstructing the dendritic arborization of individual GFP+ neurons using confocal microscopy. Similar to neurons expressing DISC1-shRNA, GFP+ neurons overexpressing KIAA1212 exhibited accelerated dendritic growth at 14 dpi (Figure 5A), as shown by a significant increase in the total dendritic length (Figure 5B). GFP+ neurons expressing CA-AKT or PTEN-shRNA also exhibited significantly accelerated dendritic growth (Figures 5A and 5B). Sholl analysis further showed much increased dendritic complexity of these newborn neurons at 14 dpi (Figure 5C). Among these manipulations, CA-AKT overexpression led to the largest increase of dendritic growth. Such a stronger effect on the maturation of newborn neurons, including both dendritic development (Figure 5) and soma size (Figure 4B), is consistent with the role of AKT as a downstream effector in the DISC1 signaling cascade. Taken together, these results further support our model that DISC1 regulates AKT signaling through KIAA1212 during development of new neurons in the adult brain.
