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Rho-associated protein kinase regulates subcellular localisation of Angiomotin and Hippo-signalling during preimplantation mouse embryo development
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SYSNO ASEP 0465273 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Rho-associated protein kinase regulates subcellular localisation of Angiomotin and Hippo-signalling during preimplantation mouse embryo development Author(s) Mihajlović, A. I. (CZ)
Bruce, Alexander (BC-A) RIDNumber of authors 2 Source Title Reproductive BioMedicine Online - ISSN 1472-6483
Roč. 33, č. 3 (2016), s. 381-390Number of pages 10 s. Language eng - English Country GB - United Kingdom Keywords Angiomotin ; Hippo-signalling ; polarization Subject RIV EB - Genetics ; Molecular Biology Institutional support BC-A - RVO:60077344 UT WOS 000386589100007 EID SCOPUS 84989807909 DOI 10.1016/j.rbmo.2016.06.028 Annotation The differential activity of the Hippo-signalling pathway between the outer- and inner-cell populations of the developing preimplantation mouse embryo directs appropriate formation of trophectoderm and inner cell mass (ICM) lineages. Such distinct signalling activity is under control of intracellular polarization, whereby Hippo-signalling is either supressed in polarized outer cells or activated in apolar inner cells. The central role of apical-basolateral polarization to such differential Hippo-signalling regulation prompted us to reinvestigate the role of potential upstream molecular regulators affecting apical-basolateral polarity. This study reports that the chemical inhibition of Rho-associated kinase (Rock) is associated with failure to form morphologically distinct blastocysts, indicative of compromised trophectoderm differentiation, and defects in the localization of both apical and basolateral polarity factors associated with malformation of tight junctions. Moreover, Rock-inhibition mediates mislocalization of the Hippo-signalling activator Angiomotin (Amot), to the basolateral regions of outer cells and is concomitant with aberrant activation of the pathway. The Rock-inhibition phenotype is mediated by Amot, as RNAi-based Amot knockdown totally rescues the normal suppression of Hippo-signalling in outer cells. In conclusion, Rock, via regulating appropriate apical-basolateral polarization in outer cells, regulates the appropriate activity of the Hippo-signalling pathway, by ensuring correct subcellular localization of Amot protein in outer cells. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2017 Electronic address http://www.sciencedirect.com/science/article/pii/S1472648316304047
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