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

Noriyuki Nishioka; Ken-ichi Inoue; Kenjiro Adachi; Hiroshi Kiyonari; Mitsunori Ota; Amy Ralston; Norikazu Yabuta; Shino Hirahara; Robert O Stephenson; Narumi Ogonuki; Ryosuke Makita; Hiroki Kurihara; Elizabeth M Morin-Kensicki; Hiroshi Nojima; Janet Rossant; Kazuki Nakao; Hitoshi Niwa; Hiroshi Sasaki

doi:10.1016/j.devcel.2009.02.003

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

Dev Cell. 2009 Mar;16(3):398-410. doi: 10.1016/j.devcel.2009.02.003.

Authors

Noriyuki Nishioka¹, Ken-ichi Inoue, Kenjiro Adachi, Hiroshi Kiyonari, Mitsunori Ota, Amy Ralston, Norikazu Yabuta, Shino Hirahara, Robert O Stephenson, Narumi Ogonuki, Ryosuke Makita, Hiroki Kurihara, Elizabeth M Morin-Kensicki, Hiroshi Nojima, Janet Rossant, Kazuki Nakao, Hitoshi Niwa, Hiroshi Sasaki

Affiliation

¹ Laboratory for Embryonic Induction, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.

PMID: 19289085
DOI: 10.1016/j.devcel.2009.02.003

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Blastocyst Inner Cell Mass / metabolism*
CDX2 Transcription Factor
Cell Cycle Proteins
Cells, Cultured
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Ectoderm / metabolism
Embryo Culture Techniques
Embryonic Stem Cells / metabolism
Female
Gene Expression Regulation, Developmental
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Mutant Strains
Mice, Transgenic
Models, Biological
Muscle Proteins / genetics
Muscle Proteins / metabolism*
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Pregnancy
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Signal Transduction
TEA Domain Transcription Factors
Transcription Factors / genetics
Transcription Factors / metabolism*
Trophoblasts / metabolism*
YAP-Signaling Proteins

Substances

Adaptor Proteins, Signal Transducing
CDX2 Transcription Factor
Cdx2 protein, mouse
Cell Cycle Proteins
DNA-Binding Proteins
Homeodomain Proteins
Muscle Proteins
Phosphoproteins
TEA Domain Transcription Factors
Tead4 protein, mouse
Transcription Factors
YAP-Signaling Proteins
Yap1 protein, mouse
Lats1 protein, mouse
Protein Serine-Threonine Kinases