Cytokinesis and postabscission midbody remnants are regulated during mammalian brain development

Abstract

Building a brain of the proper size and structure requires neural stem cells (NSCs) to divide with tight temporal and spatial control to produce different daughter cell types in proper numbers and sequence. Mammalian NSCs in the embryonic cortex must maintain their polarized epithelial structure as they undergo both early proliferative divisions and later neurogenic divisions. To do this, they undergo a polarized form of cytokinesis at the apical membrane that is not well understood. Here, we investigate whether polarized furrowing and abscission in mouse NSCs are regulated differently at earlier and later stages and in a cytokinesis mutant, Kif20b. This mutant was previously shown to have microcephaly and elevated apoptosis of NSCs. We developed methods to live image furrow ingression and midbody abscission in NSCs within cortical explants. We find that polarized furrow ingression occurs at a steady rate and completes in ∼15 min at two different ages. However, ingression is slower in a subset of Kif20b mutant NSCs. Abscission is usually observed on both sides of the midbody and takes 65 to 75 min to complete. Surprisingly, abscission is accelerated in the Kif20b mutant NSCs. Postabscission midbody remnants are observed at the apical membranes of daughter cells and are much more abundant in early-stage cortices. After NSC divisions in vitro, midbody remnants are more often retained on the daughter cells of early proliferative divisions. Altogether, these results suggest that regulation of abscission timing and midbody remnants in embryonic NSCs may influence proper brain growth and structure.