Abstract
During retinal development, neuroepithelial progenitor cells divide in either a symmetric proliferative mode, where both daughter cells remain mitotic, or in a neurogenic mode, where at least one daughter cell exits the cell cycle and differentiates as a neuron. While the cellular mechanisms of neurogenesis remain unknown, heterogeneity in cell behaviors has been postulated to influence this cell fate. I will present experiments from our lab analyzing interkinetic nuclear migration, the apical-basal movement of nuclei in phase with the cell cycle, and describe relationships of this cell behavior to neurogenesis. Using time-lapse imaging in zebrafish we find that various parameters of interkinetic nuclear migration are significantly heterogeneous among retinal neuroepithelial cells. Of significance, neurogenic progenitors have greater basal nuclei migrations during the last cell cycle preceding a terminal mitosis. In addition, we show that aPKC-mediated cell polarity is essential for the relationship between nuclear position and neurogenesis. Loss of aPKC also resulted in increased proliferative cell divisions and reduced retinal neurogenesis. Cumulatively, our data supports a novel model for neurogenesis where interkinetic nuclear migration differentially positions nuclei in neuroepithelial cells and therefore influences selection of progenitors for cell cycle exit based on apical-basal polarized signals.