The interaction between Shroom3 and Rho-kinase is required for neural tube morphogenesis in mice

Das, Debamitra; Zalewski, Jenna K.; Mohan, Swarna; Plageman, Timothy F.; VanDemark, Andrew P.; Hildebrand, Jeffrey D.

doi:10.1242/bio.20147450

Cited by 42 publications

(55 citation statements)

References 97 publications

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“…Because apical constriction is known to generate actomyosindependent tension (Martin and Goldstein, 2014), we examined whether Wtip distribution is modulated by Shroom3, which induces ectopic apical constriction in Xenopus ectoderm (Haigo et al, 2003) by recruiting Rho-associated kinase to apical junctions (Das et al, 2014;Nishimura and Takeichi, 2008). In ectodermal cells overexpressing Shroom3, the punctate localization of HA-RFP-Wtip at the junctions was rearranged into a continuous pattern ( Fig.…”

Section: Wtip Junctional Localization Is Altered In a Tension-dependementioning

confidence: 99%

The Ajuba family protein Wtip regulates actomyosin contractility during vertebrate neural tube closure

Chu

Xiang

Ossipova

et al. 2018

Journal of Cell Science

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Ajuba family proteins are implicated in the assembly of cell junctions and have been reported to antagonize Hippo signaling in response to cytoskeletal tension. To assess the role of these proteins in actomyosin contractility, we examined the localization and function of Wtip, a member of the Ajuba family, in early embryos. Targeted depletion of Wtip inhibited apical constriction in neuroepithelial cells and elicited neural tube defects. Fluorescent protein-tagged Wtip showed predominant punctate localization along the cell junctions in the epidermis and a linear junctional pattern in the neuroectoderm. In cells undergoing Shroom3-induced apical constriction, the punctate distribution was reorganized into a linear pattern. Conversely, the linear junctional pattern of Wtip in neuroectoderm changed to a more punctate distribution in cells with reduced myosin II activity. The C-terminal fragment of Wtip physically associated with Shroom3 and interfered with Shroom3 activity and neural fold formation. We therefore propose that Wtip is a tension-sensitive cytoskeletal adaptor that regulates apical constriction during vertebrate neurulation.This article has an associated First Person interview with the first author of the paper.

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Section: Wtip Junctional Localization Is Altered In a Tension-dependementioning

confidence: 99%

The Ajuba family protein Wtip regulates actomyosin contractility during vertebrate neural tube closure

Chu

Xiang

Ossipova

et al. 2018

Journal of Cell Science

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“…Shroom3 is also involved in the apical recruitment within the neuroepithelium of actin, myosin II (Hildebrand, ) and Rho‐kinase (Nishimura & Takeichi, ; Das et al. ). This is suggested to produce an apical molecular scaffold that drives tissue bending by inducing the wedge‐like shape of cells in the amphibian neural plate.…”

Section: Mts In Neuroepithelial Cell Shape Changementioning

confidence: 99%

“…This c-tubulin redistribution was found to depend on the actin-binding protein Shroom3, the knockdown of which caused paraxial MT arrays to be lost, and both apico-basal elongation and apical constriction to fail. Shroom3 is also involved in the apical recruitment within the neuroepithelium of actin, myosin II (Hildebrand, 2005) and Rhokinase (Nishimura & Takeichi, 2008;Das et al 2014). This is suggested to produce an apical molecular scaffold that drives tissue bending by inducing the wedge-like shape of cells in the amphibian neural plate.…”

Section: Mts In Neuroepithelial Cell Shape Changementioning

confidence: 99%

Microtubules, polarity and vertebrate neural tube morphogenesis

et al. 2016

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Microtubules (MTs) are key cellular components, long known to participate in morphogenetic events that shape the developing embryo. However, the links between the cellular functions of MTs, their effects on cell shape and polarity, and their role in large-scale morphogenesis remain poorly understood. Here, these relationships were examined with respect to two strategies for generating the vertebrate neural tube: bending and closure of the mammalian neural plate; and cavitation of the teleost neural rod. The latter process has been compared with 'secondary' neurulation that generates the caudal spinal cord in mammals. MTs align along the apico-basal axis of the mammalian neuroepithelium early in neural tube closure, participating functionally in interkinetic nuclear migration, which indirectly impacts on cell shape. Whether MTs play other functional roles in mammalian neurulation remains unclear. In the zebrafish, MTs are important for defining the neural rod midline prior to its cavitation, both by localizing apical proteins at the tissue midline and by orienting cell division through a mirrorsymmetric MT apparatus that helps to further define the medial localization of apical polarity proteins. Par proteins have been implicated in centrosome positioning in neuroepithelia as well as in the control of polarized morphogenetic movements in the neural rod. Understanding of MT functions during early nervous system development has so far been limited, partly by techniques that fail to distinguish 'cause' from 'effect'. Future developments will likely rely on novel ways to selectively impair MT function in order to investigate the roles they play.

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“…ROCK1 is a serine/threonine kinase whose activity drives cytoskeletal regulation associated with apical constriction (Das et al 2014; Haigo et al 2003; Hildebrand 2005). SHROOM3 can regulate NTC through interactions with the SBD domain of ROCK1 in vertebrates (Das et al 2014; Hildebrand 2005), indicating that SHROOM2 may have similar molecular activities. Moreover, we verified that these two damaging variants (p.A1331S and p.R1557H) in SHROOM2 significantly decreased the interaction between SHROOM2 and ROCK1 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…SHROOM3 can directly interact with Rho kinase (ROCK) through the ASD2 domain (Nishimura and Takeichi 2008), which is highly conserved in the SHROOM gene family (Hildebrand and Soriano 1999). Finally, the interaction between SHROOM3 and ROCK plays a pivotal role during neural tube morphogenesis (Das et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Genetic and functional analysis of SHROOM1-4 in a Chinese neural tube defect cohort

et al. 2018

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Neural tube defects (NTDs), which include spina bifida and anencephaly, are the second most common form of human structural congenital malformations. While it is well established that SHROOM3 plays a pivotal role in the complex morphogenetic processes involved in neural tube closure (NTC), the underlying genetic contributions of SHROOM gene family members in the etiology of human NTDs remain poorly understood. Herein, we systematically investigated the mutation patterns of SHROOM1-4 in a Chinese population composed of 343 NTD cases and 206 controls, using targeted next-generation sequencing. Functional variants were further confirmed by western blot and the mammalian two-hybrid assays. Loss of function (LoF) variants were identified in SHROOM3. We observed 1.56 times as many rare [minor allele frequency (MAF) < 0.01] coding variants (p = 2.9 × 10−3) in SHROOM genes, and 4.5 times as many rare D-Mis (deleterious missense) variants in SHROOM2 genes in the NTD cases compared with the controls. D-Mis variants of SHROOM2 (p.A1331S; p.R1557H) were confirmed by Sanger sequencing, and these variants were determined to have profound effects on gene function that disrupted their binding with ROCK1 in vitro. These findings provide genetic and molecular insights into the effects of rare damaging variants in SHROOM2, indicating that such variants of SHROOM2 might contribute to the risk of human NTDs. This research enhances our understanding of the genetic contribution of the SHROOM gene family to the etiology of human NTDs.

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The interaction between Shroom3 and Rho-kinase is required for neural tube morphogenesis in mice

Cited by 42 publications

References 97 publications

The Ajuba family protein Wtip regulates actomyosin contractility during vertebrate neural tube closure

The Ajuba family protein Wtip regulates actomyosin contractility during vertebrate neural tube closure

Microtubules, polarity and vertebrate neural tube morphogenesis

Genetic and functional analysis of SHROOM1-4 in a Chinese neural tube defect cohort

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