Interkinetic Nuclear Migration of Neural Progenitor Cells: Understanding Cellular Migration in Tissue Based on Live Imaging and Modeling
Department of Anatomy, Kawasaki Medical School
Abstract: Recent advances of light microscopy and tissue culturing allow us to observe cellular behavior in an intact tissue. In this article, such methods and novel concept of cellular migration are presented by introducing following study, analyzing the apical-basal nuclear oscillation in polarized neural progenitor cells in the developing brain. Known as interkinetic nuclear migration (INM), these movements are synchronized with the cell cycle such that nuclei move basally during G1 phase and apically during G2 phase. However, it is unknown how the direction of movement and the cell cycle are tightly coupled. Our study demonstrates that INM proceeds through the cell cycle-dependent linkage of cell-autonomous and non-autonomous mechanisms. The microtubule-associated protein Tpx2 links cell cycle progression and autonomous apical nuclear migration by promoting nuclear migration by altering microtubule organization during G2 phase. In contrast, in vivo observations of implanted microbeads and computational modeling imply that the basal migration of G1 phase nuclei depends on a “crowding effect” by G2 phase nuclei migrating apically. The proposed model for INM explains how the dynamics of neural progenitors harmonize their extensive proliferation with the epithelial architecture in the developing brain.
Key words: Nuclear migration, Quantitative time-lapse imaging, Simulation, Brain development, Neurogenesis