Hindbrain neuropore tissue geometry determines asymmetric cell-mediated closure dynamics in mouse embryos

Maniou, E; Staddon, MF; Marshall, AR; Greene, NDE; Copp, AJ; Banerjee, S; Galea, GL

Abstract

Gap closure is a common morphogenetic process. In mammals, failure to close the embryonic hindbrain neuropore (HNP) gap causes fatal anencephaly. We observed that surface ectoderm cells surrounding the mouse HNP assemble high-tension actomyosin purse strings at their leading edge and establish the initial contacts across the embryonic midline. Fibronectin and laminin are present, and tensin 1 accumulates in focal adhesion-like puncta at this leading edge. The HNP gap closes asymmetrically, faster from its rostral than caudal end, while maintaining an elongated aspect ratio. Cellbased physical modeling identifies two closure mechanisms sufficient to account for tissue-level HNP closure dynamics: pursestring contraction and directional cell motion implemented through active crawling. Combining both closure mechanisms hastens gap closure and produces a constant rate of gap shortening. Purse-string contraction reduces, whereas crawling increases gap aspect ratio, and their combination maintains it. Closure rate asymmetry can be explained by asymmetric embryo tissue geometry, namely a narrower rostral gap apex, whereas biomechanical tension inferred from laser ablation is equivalent at the gaps' rostral and caudal closure points. At the cellular level, the physical model predicts rearrangements of cells at the HNP rostral and caudal extremes as the gap shortens. These behaviors are reproducibly live imaged in mouse embryos. Thus, mammalian embryos coordinate cellularand tissue-level mechanics to achieve this critical gap closure event.

Citation

Maniou, E., Staddon, M., Marshall, A., Greene, N., Copp, A., Banerjee, S., & Galea, G. (2021). Hindbrain neuropore tissue geometry determines asymmetric cell-mediated closure dynamics in mouse embryos. Proceedings of the National Academy of Sciences, 118(19), https://doi.org/10.1073/pnas.2023163118

• Journal Article Type: Article
• Acceptance Date: Mar 31, 2021
• Publication Date: 2021
• Deposit Date: Dec 21, 2021
• Print ISSN: 0027-8424
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 118
• Issue: 19
• DOI: https://doi.org/10.1073/pnas.2023163118
• Keywords: neural tube; hindbrain neuropore; mouse; biomechanics; physical modeling; NEURAL-TUBE CLOSURE; DORSAL CLOSURE; EPITHELIAL CLOSURE; NONNEURAL ECTODERM; ACTIN CABLE; MORPHOGENESIS; MECHANICS; POLARITY; DEFECTS; FORCES
• Public URL: https://rvc-repository.worktribe.com/output/1553830