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Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis

Epithelial organ morphogenesis involves sequential acquisition of apicobasal polarity by epithelial cells and development of a functional lumen. In vivo, cells perceive signals from components of the extracellular matrix (ECM), such as laminin and collagens, as well as sense physical conditions, suc...

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Detalles Bibliográficos
Autores principales: Rodríguez-Fraticelli, Alejo E., Auzan, Muriel, Alonso, Miguel A., Bornens, Michel, Martín-Belmonte, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444774/
https://www.ncbi.nlm.nih.gov/pubmed/22965908
http://dx.doi.org/10.1083/jcb.201203075
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author Rodríguez-Fraticelli, Alejo E.
Auzan, Muriel
Alonso, Miguel A.
Bornens, Michel
Martín-Belmonte, Fernando
author_facet Rodríguez-Fraticelli, Alejo E.
Auzan, Muriel
Alonso, Miguel A.
Bornens, Michel
Martín-Belmonte, Fernando
author_sort Rodríguez-Fraticelli, Alejo E.
collection PubMed
description Epithelial organ morphogenesis involves sequential acquisition of apicobasal polarity by epithelial cells and development of a functional lumen. In vivo, cells perceive signals from components of the extracellular matrix (ECM), such as laminin and collagens, as well as sense physical conditions, such as matrix stiffness and cell confinement. Alteration of the mechanical properties of the ECM has been shown to promote cell migration and invasion in cancer cells, but the effects on epithelial morphogenesis have not been characterized. We analyzed the effects of cell confinement on lumen morphogenesis using a novel, micropatterned, three-dimensional (3D) Madin-Darby canine kidney cell culture method. We show that cell confinement, by controlling cell spreading, limits peripheral actin contractility and promotes centrosome positioning and lumen initiation after the first cell division. In addition, peripheral actin contractility is mediated by master kinase Par-4/LKB1 via the RhoA–Rho kinase–myosin II pathway, and inhibition of this pathway restores lumen initiation in minimally confined cells. We conclude that cell confinement controls nuclear–centrosomal orientation and lumen initiation during 3D epithelial morphogenesis.
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spelling pubmed-34447742013-03-17 Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis Rodríguez-Fraticelli, Alejo E. Auzan, Muriel Alonso, Miguel A. Bornens, Michel Martín-Belmonte, Fernando J Cell Biol Research Articles Epithelial organ morphogenesis involves sequential acquisition of apicobasal polarity by epithelial cells and development of a functional lumen. In vivo, cells perceive signals from components of the extracellular matrix (ECM), such as laminin and collagens, as well as sense physical conditions, such as matrix stiffness and cell confinement. Alteration of the mechanical properties of the ECM has been shown to promote cell migration and invasion in cancer cells, but the effects on epithelial morphogenesis have not been characterized. We analyzed the effects of cell confinement on lumen morphogenesis using a novel, micropatterned, three-dimensional (3D) Madin-Darby canine kidney cell culture method. We show that cell confinement, by controlling cell spreading, limits peripheral actin contractility and promotes centrosome positioning and lumen initiation after the first cell division. In addition, peripheral actin contractility is mediated by master kinase Par-4/LKB1 via the RhoA–Rho kinase–myosin II pathway, and inhibition of this pathway restores lumen initiation in minimally confined cells. We conclude that cell confinement controls nuclear–centrosomal orientation and lumen initiation during 3D epithelial morphogenesis. The Rockefeller University Press 2012-09-17 /pmc/articles/PMC3444774/ /pubmed/22965908 http://dx.doi.org/10.1083/jcb.201203075 Text en © 2012 Rodríguez-Fraticelli 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/).
spellingShingle Research Articles
Rodríguez-Fraticelli, Alejo E.
Auzan, Muriel
Alonso, Miguel A.
Bornens, Michel
Martín-Belmonte, Fernando
Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis
title Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis
title_full Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis
title_fullStr Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis
title_full_unstemmed Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis
title_short Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis
title_sort cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444774/
https://www.ncbi.nlm.nih.gov/pubmed/22965908
http://dx.doi.org/10.1083/jcb.201203075
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