Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis
| Autor: | Muriel Auzan, Miguel A. Alonso, Fernando Martín-Belmonte, Michel Bornens, Alejo E. Rodriguez-Fraticelli |
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| Přispěvatelé: | Human Frontier Science Program, European Commission, Ministerio de Ciencia e Innovación (España), Ministerio de Economía y Competitividad (España) |
| Rok vydání: | 2012 |
| Předmět: |
Centrosome
0303 health sciences Cell division Morphogenesis Lumen (anatomy) Epithelial Cells Cell migration Cell Communication Cell Biology Biology Article Cell biology Extracellular matrix 03 medical and health sciences 0302 clinical medicine Cell polarity Animals Laminin Research Articles 030217 neurology & neurosurgery 030304 developmental biology Epithelial polarity |
| Zdroj: | The Journal of Cell Biology Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 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. © 2012 Rodríguez-Fraticelli et al. Human Frontiers Science Program; Marie Curie, Ministerio de Ciencia e Innovación; CONSOLIDER |
| Databáze: | OpenAIRE |
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