[P1.08]: Neural precursor cell proliferation and differentiation: Looking at the redox environment and cell defense mechanisms

Static observations suggested that higher radial migration rates of postmitotic neurons are correlated with higher proliferation rates of precursors in area 17 compared to area 18 in the primate (Lukaszewicz et al., 2006). p27kip1, which is differentially expressed in these two areas (1), is one candidate to coordinate proliferation and migration. Nuclear p27kip1 interacts with CyclinE/Cdk2 complexes via its N-term domain while the C-term domain of cytoplasmic p27kip1 interacts with the RhoA GTPase, influencing cytoskeletal organisation and migration (Nguyen et al., 2006). Here our objective is to characterise the dynamics of (i) interkinetic nuclear migration (INM) of precursors and (ii) radial migration of postmitotic neurons in area 17 and area 18, in relation to areaspecific p27kip1 expression levels and its pleiotropic action on cell-cycle and cytoskeleton machineries. Biphotonic videomicroscopy analysis of migration kinetics of GFP expressing cells on organotypic slices of primate and mouse embryonic cortex. Targeted GFP labelling of precursors, downmodulation and forced expression of WT and mutant p27kip1 (p27CK-, p27S10A, p27QM) through retroviral infection and focal electroporation. Confocal quantification of nuclear and cytoplasmic p27kip1 protein expression levels. Faster INM and higher radial migration kinetics were observed in area 17 when proliferation rates are higher than in area 18. p27kip1 modulation in mouse precursors revealed that its interaction with the RhoA pathway influences both the INM of cycling precursors and radial migration of postmitotic neurons. These results point to proliferation, INM and post-mitotic radial migration being coordinated, and area-specifically regulated, through p27kip1 action on both cell cycle and cytoskeleton pathways. References: