Speaker
Description
Neural tube closure in mammals requires the sealing of the hindbrain neuropore (HNP) gap. Failure in this critical process results in fatal birth defects. Yet, the physical forces orchestrating this morphogenetic event at the cellular and tissue level have remained elusive.
Here, we combine live and fixed imaging of mouse embryos with cell-based computational modeling to investigate the mechanisms underlying mouse HNP closure. We find that two force-generating mechanisms drive HNP closure: a high-tension actomyosin purse-string acting along
the gap edge and directional cell migration. While together these reproduce gap-level dynamics, they are insufficient to explain the reproducible pattern of cell elongation along the gap border.
We show that a mechanical feedback loop between shear stress and cytoskeletal organization, where the purse-string serves as a mechanical cue, generates the observed morphological pattern around the gap. Over time, cell neighbor exchanges stall and the tissue solidifies, helping preserve cell shapes and their relative arrangements even away from the high-tension cue. This induces mechanical memory, leading to rostro-caudal midline cell elongation, consistent with observations in both the cranial and spinal mouse regions. We validate this feedback model by comparing mouse to chick embryos, which naturally lack the purse-string.
Bibliography
[1] Pérez-Verdugo, F., Maniou, E., Galea, G.L., and Banerjee, S. Mechanosensitive Feedback
Organizes Cell Shape and Motion During Hindbrain Neuropore Morphogenesis. Current
Biology, to be published.
[2] Maniou, E., Staddon, M.F., Marshall, A.R., Greene, N.D., Copp, A.J., Banerjee, S., and
Galea, G.L. (2021). Hindbrain neuropore tissue geometry determines asymmetric cell-mediated
closure dynamics in mouse embryos. Proceedings of the National Academy of Sciences 118,
e2023163118. https://doi.org/10.1073/pnas.2023163118.
