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p38 (Mapk14/11) occupies a regulatory node governing entry into primitive endoderm differentiation during preimplantation mouse embryo development
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SYSNO ASEP 0465258 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title p38 (Mapk14/11) occupies a regulatory node governing entry into primitive endoderm differentiation during preimplantation mouse embryo development Author(s) Thamodaran, V. (CZ)
Bruce, Alexander (BC-A) RIDNumber of authors 2 Article number 160190 Source Title Open Biology. - : Royal Society Publishing
Roč. 6, č. 9 (2016)Number of pages 20 s. Language eng - English Country GB - United Kingdom Keywords preimplantation mouse embryo ; cell-fate ; primitive endoderm Subject RIV EB - Genetics ; Molecular Biology Institutional support BC-A - RVO:60077344 UT WOS 000385434300009 EID SCOPUS 84990966206 DOI 10.1098/rsob.160190 Annotation During mouse preimplantation embryo development, the classically described second cell-fate decision involves the specification and segregation, in blastocyst inner cell mass (ICM), of primitive endoderm (PrE) from pluripotent epiblast (EPI). The active role of fibroblast growth factor (Fgf) signalling during PrE differentiation, particularly in the context of Erk1/2 pathway activation, is well described. However, we report that p38 family mitogen-activated protein kinases (namely p38 alpha/Mapk14 and p38 beta/Mapk11; referred to as p38-Mapk14/11) also participate in PrE formation. Specifically, functional p38-Mapk14/11 are required, during early-blastocyst maturation, to assist uncommitted ICM cells, expressing both EPI and earlier PrE markers, to fully commit to PrE differentiation. Moreover, functional activation of p38-Mapk14/11 is, as reported for Erk1/2, under the control of Fgf-receptor signalling, plus active Tak1 kinase (involved in non-canonical bone morphogenetic protein (Bmp)-receptor-mediated PrE differentiation). However, we demonstrate that the critical window of p38-Mapk14/11 activation precedes the E3.75 timepoint (defined by the initiation of the classical 'salt and pepper' expression pattern of mutually exclusive EPI and PrE markers), whereas appropriate lineage maturation is still achievable when Erk1/2 activity (via Mek1/2 inhibition) is limited to a period after E3.75. We propose that active p38-Mapk14/11 act as enablers, and Erk1/2 as drivers, of PrE differentiation during ICM lineage specification and segregation. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2017 Electronic address http://rsob.royalsocietypublishing.org/content/6/9/160190
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