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

• DOI: 10.1038/ng.173
• Publication Date: 2008-06-08T17:23:15Z
• Authors: Chi-Wei Lu; Akiko Yabuuchi; Lingyi Chen; Srinivas Viswanathan; Kitai Kim; George Q Daley
• Keywords: Flavonoids; Mitogen-Activated Protein Kinase Kinases; 0303 health sciences; Chimera; Embryonic Development; Mice, Transgenic; Embryo, Mammalian; Mice, Inbred C57BL; Proto-Oncogene Proteins p21(ras); Mice; 03 medical and health sciences; Blastocyst; Pregnancy; Ectoderm; Nitriles; Butadienes; Animals; Female; Cells, Cultured; Embryonic Stem Cells; Signal Transduction

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.