[P2.36]: ZFP423 cooperates with NICD in the activation of Hes5 gene expression

thinner cortex due to fewer numbers of mature neurons and an increase in gliogenesis. The Erk2 cKO also exhibits a deficit in learning and memory. Detailed behavioural analysis of the Erk2 cKO also revealed that the mice are anosmic. Here we describe a novel mouse model in which both Erk isoforms are inactivated in developing telencephalon. Simultaneous silencing of Erk1 and Erk2 exacerbates the Erk2 cortical phenotype. At E14.5 proliferating NPCs within Erk1/2 DKO animals exhibit decreased BrdU incorporation and almost complete loss of mitotic abventricular intermediate progenitor cells. These changes correlate with a decrease in Map2+ neurons and an increase in uncommitted Nestin+ NPCs in the VZ. Importantly, at E16.5we see an even greater exacerbation of proliferation and differentiation defects during neurogenesis due to a lack of compensation from Erk1. The perturbations of NPC cell cycle dynamics are associated with the disregulation of CyclinD1 and P27 expression; both are downstream effectors of Erk1/2. These data document a critical role of Erk1/2 in regulating neuronal progenitor cells dynamics and cortical development.