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      Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium

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          Abstract

          Cellular rearrangements between olfactory cells and supporting cells, driven by the different expression and distribution of nectins and cadherins, are required for mosaic cellular patterning in the olfactory epithelium.

          Abstract

          In the olfactory epithelium (OE), olfactory cells (OCs) and supporting cells (SCs), which express different cadherins, are arranged in a characteristic mosaic pattern in which OCs are enclosed by SCs. However, the mechanism underlying this cellular patterning is unclear. Here, we show that the cellular pattern of the OE is established by cellular rearrangements during development. In the OE, OCs express nectin-2 and N-cadherin, and SCs express nectin-2, nectin-3, E-cadherin, and N-cadherin. Heterophilic trans-interaction between nectin-2 on OCs and nectin-3 on SCs preferentially recruits cadherin via α-catenin to heterotypic junctions, and the differential distributions of cadherins between junctions promote cellular intercalations, resulting in the formation of the mosaic pattern. These observations are confirmed by model cell systems, and various cellular patterns are generated by the combinatorial expression of nectins and cadherins. Collectively, the synergistic action of nectins and cadherins generates mosaic pattern, which cannot be achieved by a single mechanism.

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          Most cited references34

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          The differential adhesion hypothesis: a direct evaluation.

          The differential adhesion hypothesis (DAH), advanced in the 1960s, proposed that the liquid-like tissue-spreading and cell segregation phenomena of development arise from tissue surface tensions that in turn arise from differences in intercellular adhesiveness. Our earlier measurements of liquid-like cell aggregate surface tensions have shown that, without exception, a cell aggregate of lower surface tension tends to envelop one of higher surface tension to which it adheres. We here measure the surface tensions of L cell aggregates transfected to express N-, P- or E-cadherin in varied, measured amounts. We report that in these aggregates, in which cadherins are essentially the only cell-cell adhesion molecules, the aggregate surface tensions are a direct, linear function of cadherin expression level. Taken together with our earlier results, the conclusion follows that the liquid-like morphogenetic cell and tissue rearrangements of cell sorting, tissue spreading and segregation represent self-assembly processes guided by the diminution of adhesive-free energy as cells tend to maximize their mutual binding. This conclusion relates to the physics governing these morphogenetic phenomena and applies independently of issues such as the specificities of intercellular adhesives.
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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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              Cadherins: a molecular family important in selective cell-cell adhesion.

              M Takeichi (1989)
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                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                29 February 2016
                : 212
                : 5
                : 561-575
                Affiliations
                [1 ]Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
                [2 ]Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
                [3 ]Division of Neural Differentiation and Regeneration, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
                [4 ]Laboratory for Morphogenetic Signaling, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
                [5 ]Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan
                [6 ]Genetic Engineering Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan
                [7 ]Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
                [8 ]Department of Machine Intelligence and Systems Engineering, Akita Prefectural University, Akita 015-0055, Japan
                [9 ]Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan
                [10 ]CREST, Japan Science and Technology Agency, Kobe 650-0047, Japan
                Author notes
                Correspondence to Hideru Togashi: htogashi@ 123456med.kobe-u.ac.jp
                Article
                201509020
                10.1083/jcb.201509020
                4772500
                26929452
                62eef848-bb7b-47c2-aabb-ef623d437dc8
                © 2016 Katsunuma et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                : 03 September 2015
                : 21 January 2016
                Funding
                Funded by: Japan Society for the Promotion of Science http://dx.doi.org/10.13039/501100001691
                Award ID: 15K10782
                Award ID: 21227005
                Award ID: 21570234
                Award ID: 22111001
                Award ID: 22791599
                Award ID: 24390388
                Award ID: 24791777
                Award ID: 25111716
                Award ID: 25127710
                Award ID: 25440117
                Award ID: 25440107
                Award ID: 26540158
                Funded by: Takeda Science Foundation http://dx.doi.org/10.13039/100007449
                Categories
                Research Articles
                Article

                Cell biology
                Cell biology

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