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      Biophysics in oviduct: Planar cell polarity, cilia, epithelial fold and tube morphogenesis, egg dynamics

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          Abstract

          Organs and tissues in multi-cellular organisms exhibit various morphologies. Tubular organs have multi-scale morphological features which are closely related to their functions. Here we discuss morphogenesis and the mechanical functions of the vertebrate oviduct in the female reproductive tract, also known as the fallopian tube. The oviduct functions to convey eggs from the ovary to the uterus. In the luminal side of the oviduct, the epithelium forms multiple folds (or ridges) well-aligned along the longitudinal direction of the tube. In the epithelial cells, cilia are formed orienting toward the downstream of the oviduct. The cilia and the folds are supposed to be involved in egg transportation. Planar cell polarity (PCP) is developed in the epithelium, and the disruption of the Celsr1 gene, a PCP related-gene, causes randomization of both cilia and fold orientations, discontinuity of the tube, inefficient egg transportation, and infertility. In this review article, we briefly introduce various biophysical and biomechanical issues in the oviduct, including physical mechanisms of formation of PCP and organized cilia orientation, epithelial cell shape regulation, fold pattern formation generated by mechanical buckling, tubulogenesis, and egg transportation regulated by fluid flow. We also mention about possible roles of the oviducts in egg shape formation and embryogenesis, sinuous patterns of tubes, and fold and tube patterns observed in other tubular organs such as the gut, airways, etc.

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          Most cited references116

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          Mechanical stretch triggers rapid epithelial cell division through Piezo1

          Despite acting as a barrier for the organs they encase, epithelial cells turnover at some of the fastest rates in the body. Yet, epithelial cell division must be tightly linked to cell death to preserve barrier function and prevent tumour formation. How do the number of dying cells match those dividing to maintain constant numbers? We previously found that when epithelial cells become too crowded, they activate the stretch-activated channel Piezo1 to trigger extrusion of cells that later die 1 . Conversely, what controls epithelial cell division to balance cell death at steady state? Here, we find that cell division occurs in regions of low cell density, where epithelial cells are stretched. By experimentally stretching epithelia, we find that mechanical stretch itself rapidly stimulates cell division through activation of the same Piezo1 channel. To do so, stretch triggers cells paused in early G2 to activate calcium-dependent ERK1/2 phosphorylation that activates cyclin B transcription necessary to drive cells into mitosis. Although both epithelial cell division and cell extrusion require Piezo1 at steady state, the type of mechanical force controls the outcome: stretch induces cell division whereas crowding induces extrusion. How Piezo1-dependent calcium transients activate two opposing processes may depend on where and how Piezo1 is activated since it accumulates in different subcellular sites with increasing cell density. In sparse epithelial regions where cells divide, Piezo1 localizes to the plasma membrane and cytoplasm whereas in dense regions where cells extrude, it forms large cytoplasmic aggregates. Because Piezo1 senses both mechanical crowding and stretch, it may act as a homeostatic sensor to control epithelial cell numbers, triggering extrusion/apoptosis in crowded regions and cell division in sparse regions.
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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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              Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression.

              Control of organ size by cell proliferation and survival is a fundamental developmental process, and its deregulation leads to cancer. However, the molecular mechanism underlying organ size control remains elusive in vertebrates. In Drosophila, the Hippo (Hpo) signaling pathway controls organ size by both restricting cell growth and proliferation and promoting cell death. Here we investigated whether mammals also require the Hpo pathway to control organ size and adult tissue homeostasis. We found that Mst1 and Mst2, the two mouse homologs of the Drosophila Hpo, control the sizes of some, but not all organs, in mice, and Mst1 and Mst2 act as tumor suppressors by restricting cell proliferation and survival. We show that Mst1 and Mst2 play redundant roles, and removal of both resulted in early lethality in mouse embryos. Importantly, tumors developed in the liver with a substantial increase of the stem/progenitor cells by 6 months after removing Mst1 and Mst2 postnatally. We show that Mst1 and Mst2 were required in vivo to control Yap phosphorylation and activity. Interestingly, apoptosis induced by TNFalpha was blocked in the Mst1 and Mst2 double-mutant cells both in vivo and in vitro. As TNFalpha is a pleiotropic inflammatory cytokine affecting most organs by regulating cell proliferation and cell death, resistance to TNFalpha-induced cell death may also contribute significantly to tumor formation in the absence of Mst1 and Mst2.
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                Author and article information

                Journal
                Biophys Physicobiol
                Biophys Physicobiol
                Biophysics and Physicobiology
                The Biophysical Society of Japan (BSJ)
                2189-4779
                2019
                26 February 2019
                : 16
                : 89-107
                Affiliations
                [1 ]Division of Embryology, National Institute for Basic Biology, Okazaki, Aichi 444-8787, Japan
                [2 ]SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan
                [3 ]Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan
                [4 ]Centre for Organismal Studies, Heidelberg University, Heidelberg 69120, Germany
                [5 ]CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
                Author notes
                Corresponding authors: Hiroshi Koyama, Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan. e-mail: hkoyama@ 123456nibb.ac.jp ; Toshihiko Fujimori, Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan. e-mail: fujimori@ 123456nibb.ac.jp
                Article
                16_89
                10.2142/biophysico.16.0_89
                6435019
                30923666
                46b1b540-a4e5-4c2e-b849-3e8fed6b68ce
                2019 © The Biophysical Society of Japan

                This article is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-sa/4.0/.

                History
                : 26 October 2018
                : 29 January 2019
                Categories
                Review Article

                mechanics,pattern formation,multi-scale,tubular organ,celsr1/flamingo

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