The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass.

By Noriyuki Nishioka, Kenichi Inoue, Kenjiro Adachi, H. Kiyonari, M. Ota, A. Ralston, N. Yabuta, Shino Hirahara, R. Stephenson, N. Ogonuki and 8 more. Developmental Cell, 2009

1,058 citations recorded by the source corpus.

Outside cells of the preimplantation mouse embryo form the trophectoderm (TE), a process requiring the transcription factor Tead4. Here, we show that transcriptionally active Tead4 can induce Cdx2 and other trophoblast genes in parallel in embryonic stem cells. In embryos, the Tead4 coactivator protein Yap localizes to nuclei of outside cells, and modulation of Tead4 or Yap activity leads to changes in Cdx2 expression. In inside cells, Yap is phosphorylated and cytoplasmic, and this involves the Hippo signaling pathway component Lats. We propose that active Tead4 promotes TE development in outside cells, whereas Tead4 activity is suppressed in inside cells by cell contact- and Lats-mediated inhibition of nuclear Yap localization. Thus, differential signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0648ba4ca885cf80585a4b1b717aeba248dabd48

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In Cell Biology

1. K. Guan
2. S. Piccolo
3. Fa-Xing Yu
4. Bin Zhao
5. M. Cordenonsi
6. H. Park
7. Jung-Soon Mo
8. S. Dupont

In Molecular Biology

1. K. Guan
2. E. Olson
3. Bin Zhao
4. Fa-Xing Yu
5. S. Piccolo
6. Jennifer Nichols
7. José C. R. Silva
8. M. Cordenonsi

Citations in the corpus

• The biology of YAP/TAZ: hippo signaling and beyond. (2014, background): “Overexpression of activated YAP and TEAD, or LATS1/2 inactivation, are sufficient to induce Cdx2 expression in ICM; conversely, LATS2 overexpression suppresses Cdx2 expression in TE (156).”
• The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal (2011, positive): “And in mouse blastocysts, YAP is nuclear in outer layer cells, and cytoplasmic in the inner blastocyst layer cell”
• Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. (2015, positive): “The different distribution of YAP/TAZ in the TE and ICM results in different gene expression signatures, especially the induction of TE-specific genes, such as Cdx2 in outer cells, thus directing cell fate specification (Nishioka et al., 2009).”
• Hippo pathway regulation by cell morphology and stress fibers (2011, background): “Core Hippo pathway components are: protein kinases Mst1/2 (Hippo; Drosophila counterparts are shown in parentheses) and Lats1/2 (Warts), co-activator proteins Yap/Taz (Yorkie) and transcription factors Tead1-4 (Scalloped).”
• The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. (2010, background): “Furthermore, modulation of TEAD4–YAP expression has been implicated in cell fate determination of trophectoderm (TE) from inner cell mass (ICM) during blastocyst development in early mouse embryos (Nishioka et al. 2009).”
• Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo (2009, background): “Specification and maintenance of the trophectoderm in murine embryos are dependent upon activation of a sequence of transcription factors, including Tead4, Cdx2 and eomesodermin (Eomes) (Nishioka et al., 2009; Strumpf et al., 2005; Voss et al., 2000; Yagi et al., 2007).”
• The Hippo Pathway: Biology and Pathophysiology. (2019, background): “Consistently, YAP displays nuclear in outer cells and cytoplasmic in inner cells during early mouse embryonic development (61).”
• Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. (2012, background): “Further studies demonstrated that cell–cell junctional proteins such as the angiomotin protein complex and a-catenin inhibit YAP (Nishioka et al. 2009; Varelas et al. 2010; Chan et al. 2011; Kim et al. 2011; Schlegelmilch et al. 2011; Silvis et al. 2011; Wang et al. 2011; Zhao et al. 2011).”
• The Hippo pathway: regulators and regulations. (2013, background): “localization in blastocysts (Fig. 4C; Nishioka et al. 2009).”
• The Hippo Signaling Pathway in Development and Cancer (2010, background): “…this view, YAP null mice die at embryonic day 8.5 (Morin-Kensicki et al., 2006) and TAZ null mice are viable (Hossain et al., 2007; Tian et al., 2007; Makita et al., 2008), but mice lacking both YAP and TAZ die extremely early, before the formation of 16-cell morula embryos (Nishioka et al., 2009).”
• The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. (2010, background): “This Hippo pathwaydependent nuclear–cytoplasmic translocation of YAP, originally observed in cell culture, has also been suggested to be responsible for the cytoplasmic translocation of YAP in inner cell mass during mouse embryo development (Nishioka et al. 2009).”
• The Hippo Signaling Pathway in Development and Disease (2019, background): “Active Hippo signaling in the inner cells leads to cytoplasmic YAP localization that promotes ICM lineage specification, while inactive Hippo signaling in outer cells results in nuclear YAP that drives TEAD4-dependent genes such as Cdx2 to specify the TE lineage (Nishioka et al., 2009).”
• FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst (2010, background): “The outside and inside cells of the blastocyst have experienced different levels of at least one other signaling pathway, the Hippo signaling pathway (Nishioka et al., 2009), suggesting that cell signaling history might lead to differential responses to FGF signals at the blastocyst stage.”