Twisting of neocortical progenitor cells underlies a spring-like mechanism for daughter-cell migration

The mammalian neocortical wall thickens extensively during embryogenesis via proliferation of progenitor cells [1-4] and migration of daughter cells toward the pial surface [5-8]. Time-lapse imaging and functional experiments were carried out so that the possible involvement of mechanical forces in these processes could be examined. When bipolar cells connecting the ventricular and pial surfaces of the mouse cerebral wall lose their ventricular attachment, they undergo somal translocation toward the outer zones, which contain differentiated neurons. The pial process of these transitioning unipolar cells exhibits a coiled or hairpin-loop morphology, suggesting that twisting and stretching of the pial process establishes a spring-like mechanism that propels the daughter cell toward the pial surface upon ventricular detachment. This model is supported by morphological changes observed in microsurgically transected pial processes. Pharmacological experiments further reveal the involvement of intermediate filaments in twisting of pial processes. These results uncover a novel mechanism for cellular migration and provide valuable tools for the detailed study of the role of mechanical forces in 3D brain development.