Study of the coupling between interkinetic nuclear migration and cell-cycle progression in the mouse developing cortex

 

The balance between proliferation and differentiation of Apical Progenitors (APs) is a crucial mechanism for proper cerebral cortex histogenesis, and its dysregulation causes important cortical malformations. In the Ventricular Zone (VZ) of the cortex, the nucleus of APs performs a stereotyped movement of Interkinetic Nuclear Migration (INM) during cell-cycle progression. This study aims to characterize the coupling between INM and cell-cycle progression. First, I present a refined description of the INM dynamics with respect to cell-cycle progression. I show that both INM and cell-cycle dynamics vary from early to late stages of corticogenesis. I have examined the impact of p27Kip1 C-terminal domain (p27-Cter) on the proliferative behavior of APs. We observed that p27-Cter expression modifies the INM as well as the distribution of APs within the cell-cycle. We evidenced that the interaction between p27Kip1 and microtubules plays a key role in the apical movement of APs. Finally, I studied the effect of CyclinE protein overexpression on the coupling between INM and cell-cycle progression. We observed that CyclinE overexpression, which decreases G1 phase duration, also impacts INM, via a modification of the velocity and directionality of the INM movements.