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

The strong increase in the size of the human neocortex is supported by a neural stem cell population, the basal radial glial (bRG) cells. Using live imaging of human fetal tissue and cortical organoids, we identify two translocation mechanisms 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 dynein motor and its activator LIS1, which are recruited to the nuclear envelope by the LINC complex, while MST is controlled by the mitotic cell-rounding pathway. Eighty-five percent of bRG cell translocation is due to IST, resulting in a total movement of 0.67 mm per month of gestation. Our work identifies how bRG cells colonize the human fetal cortex and further shows that IST and MST also occur in bRG-related glioblastoma cells.