Neuroepithelial cells balance the need for tissue growth with the morphogenetic imperative of neural tube closure. These cells undergo apical constriction to generate mechanical forces that elevate the neural folds, yet they are thought to apically dilate during mitosis. However, we previously reported that mitotic neuroepithelial cells in the mouse posterior neuropore have smaller apical surfaces than non-mitotic cells.
Here, we document a progressive apical enrichment of non-muscle myosin II in mitotic, but not non-mitotic, neuroepithelial cells, which exhibit smaller apical areas. Live imaging of the chick posterior neuropore confirms apical constriction synchronized with mitosis, reaching maximal constriction at anaphase, prior to division and subsequent redilation. The amplitude of apical constriction during mitosis is significantly greater than constrictions occurring during interphase.
To investigate whether this phenomenon is conserved in humans, we characterized early stages of induced pluripotent stem cell (iPSC) differentiation through dual SMAD inhibition, which robustly produces pseudostratified neuroepithelia with apically enriched actomyosin. These cultured neuroepithelial cells achieve apical areas equivalent to those in mouse embryos. iPSC-derived neuroepithelial cells display large apical areas in G2, which constrict in M phase and maintain this constricted state through G1/S.
Since this differentiation method yields anterior neural identity, we examined the anterior neuroepithelium of the elevating neural tube in the mouse midbrain. Rather than constricting, mitotic neuroepithelial cells in the midbrain exhibit larger apical areas than interphase cells. Tissue geometry differs between the apically convex midbrain and the flat posterior neuropore. Culturing human neuroepithelia on surfaces mimicking convex geometry prevents mitotic apical constriction.
Thus, neuroepithelial cells undergo high-amplitude apical constriction synchronized with cell cycle progression, but the timing of this constriction is influenced by tissue geometry.
