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      Planar polarization of Vangl2 in the vertebrate neural plate is controlled by Wnt and Myosin II signaling

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          Abstract

          The vertebrate neural tube forms as a result of complex morphogenetic movements, which require the functions of several core planar cell polarity (PCP) proteins, including Vangl2 and Prickle. Despite the importance of these proteins for neurulation, their subcellular localization and the mode of action have remained largely unknown. Here we describe the anteroposterior planar cell polarity (AP-PCP) of the cells in the Xenopus neural plate. At the neural midline, the Vangl2 protein is enriched at anterior cell edges and that this localization is directed by Prickle, a Vangl2-interacting protein. Our further analysis is consistent with the model, in which Vangl2 AP-PCP is established in the neural plate as a consequence of Wnt-dependent phosphorylation. Additionally, we uncover feedback regulation of Vangl2 polarity by Myosin II, reiterating a role for mechanical forces in PCP. These observations indicate that both Wnt signaling and Myosin II activity regulate cell polarity and cell behaviors during vertebrate neurulation.

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          Most cited references81

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          Non-muscle myosin II takes centre stage in cell adhesion and migration.

          Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains. The three mammalian NM II isoforms have both overlapping and unique properties. Owing to its position downstream of convergent signalling pathways, NM II is central in the control of cell adhesion, cell migration and tissue architecture. Recent insight into the role of NM II in these processes has been gained from loss-of-function and mutant approaches, methods that quantitatively measure actin and adhesion dynamics and the discovery of NM II mutations that cause monogenic diseases.
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            Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila.

            Planar cell polarity (PCP) proteins form polarized cortical domains that govern polarity of external structures such as hairs and cilia in both vertebrate and invertebrate epithelia. The mechanisms that globally orient planar polarity are not understood, and are investigated here in the Drosophila wing using a combination of experiment and theory. Planar polarity arises during growth and PCP domains are initially oriented toward the well-characterized organizer regions that control growth and patterning. At pupal stages, the wing hinge contracts, subjecting wing-blade epithelial cells to anisotropic tension in the proximal-distal axis. This results in precise patterns of oriented cell elongation, cell rearrangement and cell division that elongate the blade proximo-distally and realign planar polarity with the proximal-distal axis. Mutation of the atypical Cadherin Dachsous perturbs the global polarity pattern by altering epithelial dynamics. This mechanism utilizes the cellular movements that sculpt tissues to align planar polarity with tissue shape. Copyright 2010 Elsevier Inc. All rights reserved.
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              Planar cell polarity links axes of spatial dynamics in neural-tube closure.

              Neural-tube closure is a critical step of embryogenesis, and its failure causes serious birth defects. Coordination of two morphogenetic processes--convergent extension and neural-plate apical constriction--ensures the complete closure of the neural tube. We now provide evidence that planar cell polarity (PCP) signaling directly links these two processes. In the bending neural plates, we find that a PCP-regulating cadherin, Celsr1, is concentrated in adherens junctions (AJs) oriented toward the mediolateral axes of the plates. At these AJs, Celsr1 cooperates with Dishevelled, DAAM1, and the PDZ-RhoGEF to upregulate Rho kinase, causing their actomyosin-dependent contraction in a planar-polarized manner. This planar-polarized contraction promotes simultaneous apical constriction and midline convergence of neuroepithelial cells. Together our findings demonstrate that PCP signals confer anisotropic contractility on the AJs, producing cellular forces that promote the polarized bending of the neural plate. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Biol Open
                Biol Open
                biolopen
                bio
                Biology Open
                The Company of Biologists (Bidder Building, 140 Cowley Road, Cambridge, CB4 0DL, UK )
                2046-6390
                15 June 2015
                24 April 2015
                : 4
                : 6
                : 722-730
                Affiliations
                [1]Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai , New York, NY 10029, USA
                Author notes
                [* ]Author for correspondence ( sergei.sokol@ 123456mssm.edu )
                Article
                BIO201511676
                10.1242/bio.201511676
                4467192
                25910938
                dcbb8b49-e2ae-40d1-92b2-96f901c87cb1
                © 2015. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 1 February 2015
                : 4 March 2015
                Categories
                Research Article

                Life sciences
                planar cell polarity,vangl2,prickle,myosin ii,xenopus,neural tube closure,morphogenesis
                Life sciences
                planar cell polarity, vangl2, prickle, myosin ii, xenopus, neural tube closure, morphogenesis

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