Local and collective cellular forces driving neural tube closure

Neural tube closure in mammals requires the sealing of the hindbrain neuropore gap, a critical morphogenetic event in development. Failure in this closure process results in fatal birth defects. Yet, the cellular and tissue-level physical forces orchestrating this critical process have remained elusive. Here, we utilize live-imaging data in mouse embryos to construct a cell-based computational model of hindbrain neuropore gap closure, shedding light on the underlying physical mechanisms. We find that the coordination of two force-generating mechanisms is required to describe gap closure dynamics: actomyosin purse-string contraction at the gap border and directional active cell crawling. However, these mechanisms alone cannot account for the experimentally observed heterogeneity in cell morphologies around the gap. We show that anisotropic medial stress within border cells is required to generate the observed cell morphologies. Our model further predicts rostro-caudal elongation of midline cells and an anisotropic tension pattern surrounding the gap, consistent with measurements of the mechanoresponsive YAP nuclear localization. These findings provide a new physical framework for understanding the cellular and tissue-level mechanisms underlying hindbrain neuropore gap closure.