Two independent translocation modes drive neural stem cell dissemination into the human fetal cortex

Abstract

The strong size increase of the human neocortex is supported both by the amplification and the basal translocation of a neural stem cell population, the basal radial glial cells (or bRG cells). Using live imaging of second trimester human fetal tissue and cortical organoids, we identify two independent translocation modes for bRG cell colonization of the human neocortex. On top of an actomyosin-dependent movement called mitotic somal translocation (MST), we identify a microtubule-dependent motion occurring during interphase, that we call interphasic somal translocation (IST). We show that IST is driven by the LINC complex, through the nuclear envelope recruitment of the dynein motor and of its activator LIS1. Consequently, IST severely altered in LIS1 patient-derived cortical organoids. We also demonstrate that MST occurs during prometaphase and is a mitotic spindle translocation event. MST is controlled by the mitotic cell rounding molecular pathway, via Moesin and Vimentin, driving translocation. We report that 85% of bRG cell translocation is due to IST, for a total movement of 0,67 mm per month of human fetal gestation. Our work identifies how bRG cells colonize the human fetal cortex, and further shows that IST and MST are conserved in bRG-related migrating glioblastoma cells.