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 rost… Show more
“…Travelling waves of actomyosin contraction can propagate across the cortical surface [ 16 , 18 , 20 ], and can be highly organised as in the case of surface contraction waves, which propagate as single waves from one pole of the cell to the other [ 19 , 20 ]. In other physiological contexts, stable contractile structures are needed, as in the formation of stress fibers during cell adhesion [ 10 ], assembly of actomyosin purse-string during wound healing or gap closure [ 21 – 23 ], or the formation of a contractile ring during cytokinesis [ 24 , 25 ]. While the biochemical pathways underlying actomyosin dynamics are known, the mechanisms by which actomyosin-driven mechanical forces feedback to upstream chemical signals to govern patterns and flows in the actin cortex remain poorly understood [ 4 ].…”
The actin cortex is an active adaptive material, embedded with complex regulatory networks that can sense, generate, and transmit mechanical forces. The cortex exhibits a wide range of dynamic behaviours, from generating pulsatory contractions and travelling waves to forming organised structures. Despite the progress in characterising the biochemical and mechanical components of the actin cortex, the emergent dynamics of this mechanochemical system is poorly understood. Here we develop a reaction-diffusion model for the RhoA signalling network, the upstream regulator for actomyosin assembly and contractility, coupled to an active actomyosin gel, to investigate how the interplay between chemical signalling and mechanical forces regulate stresses and patterns in the cortex. We demonstrate that mechanochemical feedback in the cortex acts to destabilise homogeneous states and robustly generate pulsatile contractions. By tuning active stress in the system, we show that the cortex can generate propagating contraction pulses, form network structures, or exhibit topological turbulence.
“…Travelling waves of actomyosin contraction can propagate across the cortical surface [ 16 , 18 , 20 ], and can be highly organised as in the case of surface contraction waves, which propagate as single waves from one pole of the cell to the other [ 19 , 20 ]. In other physiological contexts, stable contractile structures are needed, as in the formation of stress fibers during cell adhesion [ 10 ], assembly of actomyosin purse-string during wound healing or gap closure [ 21 – 23 ], or the formation of a contractile ring during cytokinesis [ 24 , 25 ]. While the biochemical pathways underlying actomyosin dynamics are known, the mechanisms by which actomyosin-driven mechanical forces feedback to upstream chemical signals to govern patterns and flows in the actin cortex remain poorly understood [ 4 ].…”
The actin cortex is an active adaptive material, embedded with complex regulatory networks that can sense, generate, and transmit mechanical forces. The cortex exhibits a wide range of dynamic behaviours, from generating pulsatory contractions and travelling waves to forming organised structures. Despite the progress in characterising the biochemical and mechanical components of the actin cortex, the emergent dynamics of this mechanochemical system is poorly understood. Here we develop a reaction-diffusion model for the RhoA signalling network, the upstream regulator for actomyosin assembly and contractility, coupled to an active actomyosin gel, to investigate how the interplay between chemical signalling and mechanical forces regulate stresses and patterns in the cortex. We demonstrate that mechanochemical feedback in the cortex acts to destabilise homogeneous states and robustly generate pulsatile contractions. By tuning active stress in the system, we show that the cortex can generate propagating contraction pulses, form network structures, or exhibit topological turbulence.
“…A neuropore has been described for hagfish but not much further information is available due to limited knowledge of hagfish development ( Higuchi et al, 2019 , Ota and Kuratani, 2006 , Wicht, 1996 ). Overall, this early step is comparable to the keel of zebrafish neuropore formation and similar factors may influence closure of the neuropore ( Shinotsuka et al, 2018 ) in amniotes ( Copp and Greene, 2010 , Maniou et al, 2021 , Müller and O'Rahilly, 1987 , Rolo et al, 2019 ). Fig.…”
Section: Neuropore Formation Is Unique Among Chordatesmentioning
confidence: 79%
“…5 ). Formation of the neural tube starts in the hindbrain and fusion progresses anteriorly, leaving the neuropore at the last step of closure the dorsal part of the brain in gnthostomes ( Maniou et al, 2021 ). Likewise, he ‘frontal eye’ in lancelets exhibits a few sensory cells which reach out of the neuropore ( Holland, 2020 , Lacalli et al, 1994 ).…”
Section: Neuropore Formation Is Unique Among Chordatesmentioning
“…Cell geometry is now recognized as a biomechanical influence alongside active tension/compression and substrate rheology. Subtle changes in tissue curvature change the effective force direction produced by cellular contractility (Maniou et al, 2021). Forcing cultured embryo blastomeres into cylindrical rather than globoid shapes redistributes their nuclear localization of YAP (Royer et al, 2020).…”
Neuroepithelial cells multitask, balancing tissue growth with the morphogenetic imperative of closing the neural tube. They apically constrict to generate mechanical forces which elevate the neural folds, but 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 progressive apical enrichment of non-muscle myosin-II in mitotic, but not non-mitotic, neuroepithelial cells with smaller apical areas. Live-imaging of the chick posterior neuropore confirms apical constriction synchronised with mitosis, reaching maximal constriction by anaphase, before division and re-dilation. Mitotic apical constriction amplitude is significantly greater than interphase constrictions. To investigate conservation in humans, we characterised early stages of iPSC differentiation through dual SMAD-inhibition to robustly produce pseudostratified neuroepithelia with apically enriched actomyosin. These cultured neuroepithelial cells achieve an equivalent apical area to those in mouse embryos. iPSC-derived neuroepithelial cells have large apical areas in G2 which constrict in M phase and retain this constriction in G1/S. Given that this differentiation method produces anterior neural identities, we studied the anterior neuroepithelium of the elevating mouse mid-brain neural tube. Instead of constricting, mid-brain mitotic neuroepithelial cells have larger apical areas than interphase cells. Tissue geometry differs between the apically convex early midbrain and concave posterior neuropore. Culturing human neuroepithelia on equivalently convex surfaces prevents mitotic apical constriction. Thus, synchronisation of apical constriction with the cell cycle is a geometry-dependent behaviour which reverses prior dilation in mitotic neuroepithelial cells of the closing vertebrate neural tube.
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