Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos

Chi Wei Lu; Akiko Yabuuchi; Lingyi Chen; Srinivas Viswanathan; Kitai Kim; George Q. Daley

doi:10.1038/ng.173

Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos

Chi Wei Lu, Akiko Yabuuchi, Lingyi Chen, Srinivas Viswanathan, Kitai Kim, George Q. Daley

Research output: Contribution to journal › Article › peer-review

132 Scopus citations

Abstract

In blastocyst chimeras, embryonic stem (ES) cells contribute to embryonic tissues but not extraembryonic trophectoderm. Conditional activation of HRas1^Q61L in ES cells in vitro induces the trophectoderm marker Cdx2 and enables derivation of trophoblast stem (TS) cell lines that, when injected into blastocysts, chimerize placental tissues. Erk2, the downstream effector of Ras-mitogen-activated protein kinase (MAPK) signaling, is asymmetrically expressed in the apical membranes of the 8-cell-stage embryo just before morula compaction. Inhibition of MAPK signaling in cultured mouse embryos compromises Cdx2 expression, delays blastocyst development and reduces trophectoderm outgrowth from embryo explants. These data show that ectopic Ras activation can divert ES cells toward extraembryonic trophoblastic fates and implicate Ras-MAPK signaling in promoting trophectoderm formation from mouse embryos.

Original language	English (US)
Pages (from-to)	921-926
Number of pages	6
Journal	Nature genetics
Volume	40
Issue number	7
DOIs	https://doi.org/10.1038/ng.173
State	Published - Jul 2008
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics

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10.1038/ng.173

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@article{3540ea22632a4756b494b0246a5d0792,

title = "Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos",

abstract = "In blastocyst chimeras, embryonic stem (ES) cells contribute to embryonic tissues but not extraembryonic trophectoderm. Conditional activation of HRas1Q61L in ES cells in vitro induces the trophectoderm marker Cdx2 and enables derivation of trophoblast stem (TS) cell lines that, when injected into blastocysts, chimerize placental tissues. Erk2, the downstream effector of Ras-mitogen-activated protein kinase (MAPK) signaling, is asymmetrically expressed in the apical membranes of the 8-cell-stage embryo just before morula compaction. Inhibition of MAPK signaling in cultured mouse embryos compromises Cdx2 expression, delays blastocyst development and reduces trophectoderm outgrowth from embryo explants. These data show that ectopic Ras activation can divert ES cells toward extraembryonic trophoblastic fates and implicate Ras-MAPK signaling in promoting trophectoderm formation from mouse embryos.",

author = "Lu, {Chi Wei} and Akiko Yabuuchi and Lingyi Chen and Srinivas Viswanathan and Kitai Kim and Daley, {George Q.}",

note = "Funding Information: This study was supported by grants from the US National Institutes of Health and the NIH Director{\textquoteright}s Pioneer Award of the NIH Roadmap for Medical Research. G.Q.D. is a recipient of the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research. We are grateful to J. Rossant (Hospital for Sick Children, University of Toronto, Canada) for providing TS cells and experimental advice and for critical reading of this manuscript.",

year = "2008",

month = jul,

doi = "10.1038/ng.173",

language = "English (US)",

volume = "40",

pages = "921--926",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "7",

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T1 - Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos

AU - Lu, Chi Wei

AU - Yabuuchi, Akiko

AU - Chen, Lingyi

AU - Viswanathan, Srinivas

AU - Kim, Kitai

AU - Daley, George Q.

N1 - Funding Information: This study was supported by grants from the US National Institutes of Health and the NIH Director’s Pioneer Award of the NIH Roadmap for Medical Research. G.Q.D. is a recipient of the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research. We are grateful to J. Rossant (Hospital for Sick Children, University of Toronto, Canada) for providing TS cells and experimental advice and for critical reading of this manuscript.

PY - 2008/7

Y1 - 2008/7

N2 - In blastocyst chimeras, embryonic stem (ES) cells contribute to embryonic tissues but not extraembryonic trophectoderm. Conditional activation of HRas1Q61L in ES cells in vitro induces the trophectoderm marker Cdx2 and enables derivation of trophoblast stem (TS) cell lines that, when injected into blastocysts, chimerize placental tissues. Erk2, the downstream effector of Ras-mitogen-activated protein kinase (MAPK) signaling, is asymmetrically expressed in the apical membranes of the 8-cell-stage embryo just before morula compaction. Inhibition of MAPK signaling in cultured mouse embryos compromises Cdx2 expression, delays blastocyst development and reduces trophectoderm outgrowth from embryo explants. These data show that ectopic Ras activation can divert ES cells toward extraembryonic trophoblastic fates and implicate Ras-MAPK signaling in promoting trophectoderm formation from mouse embryos.

AB - In blastocyst chimeras, embryonic stem (ES) cells contribute to embryonic tissues but not extraembryonic trophectoderm. Conditional activation of HRas1Q61L in ES cells in vitro induces the trophectoderm marker Cdx2 and enables derivation of trophoblast stem (TS) cell lines that, when injected into blastocysts, chimerize placental tissues. Erk2, the downstream effector of Ras-mitogen-activated protein kinase (MAPK) signaling, is asymmetrically expressed in the apical membranes of the 8-cell-stage embryo just before morula compaction. Inhibition of MAPK signaling in cultured mouse embryos compromises Cdx2 expression, delays blastocyst development and reduces trophectoderm outgrowth from embryo explants. These data show that ectopic Ras activation can divert ES cells toward extraembryonic trophoblastic fates and implicate Ras-MAPK signaling in promoting trophectoderm formation from mouse embryos.

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Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos

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