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Angiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway-dependent and -independent mechanisms

Leung, Chuen Yan and Zernicka-Goetz, Magdalena (2013) Angiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway-dependent and -independent mechanisms. Nature Communications, 4 . Art. No. 2251. ISSN 2041-1723. PMCID PMC3741640. doi:10.1038/ncomms3251. https://resolver.caltech.edu/CaltechAUTHORS:20190405-170316805

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Abstract

Cell identity is specified in the early mammalian embryo by the generation of precursors for two cell lineages: the pluripotent inner cell mass and differentiating trophectoderm. Here we identify Angiomotin as a key regulator of this process. We show that the loss of Angiomotin, together with Angiomotin-like 2, leads to differentiation of inner cell mass cells and compromised peri-implantation development. We show that Angiomotin regulates localization of Yap, and Yap-binding motifs are required for full activity of Angiomotin. Importantly, we also show that Angiomotin function can compensate for the absence of Lats1/2 kinases, indicating the ability of Angiomotin to bypass the classical Hippo pathway for Yap regulation. In polarized outside cells, Angiomotin localizes apically, pointing to the importance of cell polarity in regulating Yap to promote differentiation. We propose that both Hippo pathway-dependent and Hippo pathway-independent mechanisms regulate Yap localization to set apart pluripotent and differentiated lineages in the pre-implantation mouse embryo.


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https://doi.org/10.1038/ncomms3251DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741640/PubMed CentralArticle
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2013 The Author(s). This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/. Received 11 March 2013. Accepted 03 July 2013. Published 01 August 2013. We thank W. Mansfield for assistance on the embryo transfer experiments and our colleagues for advice and to the Wellcome Trust for funding. Author Contributions: All experiments were performed in M.Z.G.’s laboratory by C.Y.L. The data were analysed and interpreted by C.Y.L. and M.Z.G. The manuscript was written by C.Y.L. and M.Z.G. The authors declare no competing financial interests.
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Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
PubMed Central ID:PMC3741640
DOI:10.1038/ncomms3251
Record Number:CaltechAUTHORS:20190405-170316805
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190405-170316805
Official Citation:Leung, C.Y. and Zernicka-Goetz M. Angiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway-dependent and independent mechanisms. Nat. Commun. 4:2251 doi: 10.1038/ncomms3251 (2013).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94556
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:11 Apr 2019 20:05
Last Modified:16 Nov 2021 17:05

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