title: 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.
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, the Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Chuen Yan
authors.initials: CY
authors.lastname: Leung
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D020816:Amino Acid Motifs; D000091082:Angiomotins; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000172:deficiency / Q000378:metabolism*; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C511047:Amot protein, mouse; D000091082:Angiomotins; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases
references.citation: Nat Cell Biol. 2000 Feb;2(2):70-5
references.pmid: 10655585
references.citation: FASEB J. 1998 Dec;12(15):1731-8
references.pmid: 9837863
references.citation: J Embryol Exp Morphol. 1972 Oct;28(2):263-78
references.pmid: 4674567
references.citation: Development. 2011 Sep;138(18):3907-14
references.pmid: 21831922
references.citation: Dev Biol. 2010 Aug 1;344(1):66-78
references.pmid: 20430022
references.citation: Cell. 1981 Apr;24(1):71-80
references.pmid: 7237545
references.citation: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W332-9
references.pmid: 20444868
references.citation: Blood. 2009 Jan 1;113(1):244-53
references.pmid: 18824598
references.citation: Gene. 2002 Sep 18;298(1):69-77
references.pmid: 12406577
references.citation: J Biol Chem. 2011 Mar 4;286(9):7018-26
references.pmid: 21224387
references.citation: Development. 2005 May;132(9):2093-102
references.pmid: 15788452
references.citation: J Cell Sci. 2005 Feb 1;118(Pt 3):505-15
references.pmid: 15657073
references.citation: Genes Dev. 2007 Aug 15;21(16):2055-68
references.pmid: 17699752
references.citation: Dev Cell. 2004 Jan;6(1):133-44
references.pmid: 14723853
references.citation: Cell Rep. 2012 Oct 25;2(4):756-65
references.pmid: 23041313
references.citation: Biochem J. 2011 Jun 1;436(2):213-24
references.pmid: 21568941
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6364-9
references.pmid: 20308546
references.citation: Genes Cells. 2007 Apr;12(4):473-86
references.pmid: 17397395
references.citation: Dev Cell. 2009 Mar;16(3):398-410
references.pmid: 19289085
references.citation: Biochem J. 2012 Jun 1;444(2):279-89
references.pmid: 22385262
references.citation: Cell. 2006 May 5;125(3):535-48
references.pmid: 16678097
references.citation: Genes Dev. 2008 Oct 1;22(19):2692-706
references.pmid: 18832072
references.citation: Curr Biol. 2003 Apr 1;13(7):613-7
references.pmid: 12676095
references.citation: J Biol Chem. 2011 Feb 11;286(6):4364-70
references.pmid: 21187284
references.citation: Development. 2011 Jun;138(11):2337-46
references.pmid: 21525075
references.citation: Nature. 2011 Jun 08;474(7350):179-83
references.pmid: 21654799
references.citation: Curr Opin Genet Dev. 2010 Oct;20(5):485-91
references.pmid: 20554442
references.citation: J Embryol Exp Morphol. 1967 Aug;18(1):155-80
references.pmid: 6048976
references.citation: Cell Res. 2011 Oct;21(10):1513-6
references.pmid: 21808298
references.citation: Cancer Cell. 2011 Apr 12;19(4):527-40
references.pmid: 21481793
references.citation: Genes Dev. 2011 Jan 1;25(1):51-63
references.pmid: 21205866
references.citation: Genes Dev. 2012 Jan 1;26(1):54-68
references.pmid: 22215811
references.citation: Nat Rev Genet. 2009 Jul;10(7):467-77
references.pmid: 19536196
references.citation: PLoS One. 2012;7(4):e35735
references.pmid: 22558212
references.citation: EMBO J. 2011 May 10;30(12):2325-35
references.pmid: 21556047
references.citation: J Biol Chem. 2005 Oct 14;280(41):34859-69
references.pmid: 16043488
references.citation: Cell Rep. 2013 Feb 21;3(2):442-57
references.pmid: 23375373
references.citation: FEBS J. 2006 May;273(9):2000-11
references.pmid: 16640563
references.citation: Mol Biol Cell. 2011 Oct;22(19):3725-33
references.pmid: 21832154