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Published August 1, 2013 | Supplemental Material + Published
Journal Article Open

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

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.

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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