Letter abstract
Nature Genetics 40, 921 - 926 (2008)
Published online: 8 June 2008 | doi:10.1038/ng.173
Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos
Chi-Wei Lu1,2,6, Akiko Yabuuchi1,2, Lingyi Chen1,2, Srinivas Viswanathan1,2,3, Kitai Kim1,2 & George Q Daley1,2,3,4,5
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.
- Division of Pediatric Hematology and Oncology, Children's Hospital Boston and Dana Faber Cancer Institute, Boston, Massachusetts 02115, USA.
- Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
- Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
- Howard Hughes Medical Institute.
- Present address: McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Correspondence to: George Q Daley1,2,3,4,5 e-mail: george.daley@childrens.harvard.edu
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