Biomechanical coupling facilitates spinal neural tube closure in mouse embryos

Galea, Gabriel L.; Cho, Young-June; Galea, Gauden; Molè, Matteo A.; Rolo, Ana; Savery, Dawn; Moulding, Dale; Culshaw, Lucy H.; Nikolopoulou, Evanthia; Greene, Nicholas D. E.; Copp, Andrew J.

doi:10.1073/pnas.1700934114

Cited by 102 publications

(159 citation statements)

References 64 publications

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“…Tissue contraction is a key mode of morphogenesis where force is propagated across distances that are far longer than the cell length-scale (Fernandez-Gonzalez et al, 2009;Galea et al, 2017;Hutson et al, 2003a;Martin et al, 2010;Varner and Taber, 2012). Tissue contraction can bring opposing cell sheets together, a mechanism used in both development and wound healing (Davidson et al, 2002;Kiehart et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Structural redundancy in supracellular actomyosin networks enables robust tissue folding

Yevick

Miller

Martin

2019

Preprint

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Tissue morphogenesis is strikingly reproducible. Yet, how tissues are robustly sculpted, even under challenging conditions, is unknown. Here, we combined network analysis, experimental perturbations, and computational modeling to determine how network connectivity between hundreds of contractile cells on the ventral side of the Drosophila embryo ensures robust tissue folding. We identified two network properties that mechanically promote robustness. First, redundant supracellular cytoskeletal network paths ensure global connectivity, even with network degradation. By forming many more connections than are required, morphogenesis is not disrupted by local network damage, analogous to the way redundancy guarantees the large-scale function of vasculature and transportation networks. Second, directional stiffening of edges oriented orthogonal to the folding axis promotes furrow formation at lower contractility levels. Structural redundancy and directional network stiffening ensure robust tissue folding with proper orientation.

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Section: Introductionmentioning

confidence: 99%

Structural redundancy in supracellular actomyosin networks enables robust tissue folding

Yevick

Miller

Martin

2019

Preprint

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“…Recent studies of zippering and neural tube closure in mouse embryos suggest that an actomyosin cable forms between epithelial and neuroectodermal cells, and contributes to forces that drive zippering (Galea et al, 2017). Thus it will be interesting to determine whether mechanisms similar to those we describe here also pattern myosin activity during neural tube closure in mouse embryos.…”

Section: Implications For Dynamic Control Of Zipper Progression In Asmentioning

confidence: 65%

Differential expression and homotypic enrichment of a classic Cadherin directs tissue-level contractile asymmetry during neural tube closure

Hashimoto

Munro

2018

Preprint

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Embryos pattern force generation at tissue boundaries during morphogenesis, but how they do so remains poorly understood. Here we show how tissue-specific expression of the type II cadherin, Cadherin2 (hereafter Cad2), patterns actomyosin contractility along the neural/epidermal (Ne/Epi) boundary to drive zippering and neural tube closure in the basal chordate, Ciona robusta. Cad2 is differentially expressed and homotypically enriched in neural cells along the Ne/Epi boundary, where RhoA and Myosin are activated during zipper progression. Equalizing Cad2 expression across the Ne/Epi boundary inhibits RhoA/Myosin activation and zipper progression, while creating ectopic Cad2 expression boundaries is sufficient to direct RhoA/Myosin activity to those boundaries. We show that Cad2 polarizes RhoA activity by sequestering the Rho GTPase activating protein, Gap21/23, to homotypic junctions, which in turn redirects RhoA/Myosin activity to heterotypic Ne/Epi junctions. By activating Myosin II along Ne/Epi junctions ahead of zipper and inhibiting Myosin II at new Ne/Ne junctions behind zipper, Cad2 promotes tissue level contractile asymmetry to drive zipper progression.

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“…Nuclei were labelled with TO-PRO-3 (Thermo Fisher). Images were captured on an LSM880 Examiner confocal system (Carl Zeiss Ltd, UK) as previously reported (19), and linear adjustments made using Fiji software.…”

Section: Immunofluorescencementioning

confidence: 99%

Novel mouse model of encephalocele: post-neurulation origin and relationship to open neural tube defects

Rolo

Galea

Savery

et al. 2019

Preprint

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Corresponding authors: a.copp@ucl.ac.uk and anarolo@hotmail.com Running title: Novel mouse model of encephalocele 2 SUMMARY STATEMENT Encephalocele -a severe brain defect -arises after neural tube closure, but can share a common genetic cause with anencephaly, a defect of neural tube closure. ABSTRACT Encephalocele is a clinically important birth defect that can lead to severe disability in childhood and beyond. The embryonic pathogenesis of encephalocele is poorly understood and, while usually classified as a 'neural tube defect', there is conflicting evidence on whether encephalocele results from defective neural tube closure, or is a post-neurulation defect. It is also unclear whether encephalocele can result from the same causative factors as anencephaly and open spina bifida, or whether it is aetiologically distinct. This lack of information results largely from the scarce availability of animal models of encephalocele, particularly ones that resemble the commonest, non-syndromic human defects. Here we report a novel mouse model of occipito-parietal encephalocele, in which the small GTPase Rac1 is conditionally ablated in the (non-neural) surface ectoderm. Most mutant fetuses have open spina bifida, and some also exhibit exencephaly/anencephaly. However, a large proportion of mutant fetuses exhibit encephalocele affecting the occipito-parietal region. The encephalocele phenotype does not result from a defect in neural tube closure, but rather from a later disruption of the surface ectoderm covering the already closed neural tube, allowing the brain to herniate. The neuroepithelium itself shows no down-regulation of Rac1 and appears morphologically normal until late gestation. A large skull defect develops overlying the region of brain herniation. Our work provides a new genetic model of occipitoparietal encephalocele, particularly resembling non-syndromic human cases. While encephalocele has a different, later-arising pathogenesis than open neural tube defects, both can share the same genetic causation.

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Biomechanical coupling facilitates spinal neural tube closure in mouse embryos

Cited by 102 publications

References 64 publications

Structural redundancy in supracellular actomyosin networks enables robust tissue folding

Structural redundancy in supracellular actomyosin networks enables robust tissue folding

Differential expression and homotypic enrichment of a classic Cadherin directs tissue-level contractile asymmetry during neural tube closure

Novel mouse model of encephalocele: post-neurulation origin and relationship to open neural tube defects

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