Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos.
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.
Division of Pediatric Hematology and Oncology, Children's Hospital Boston and Dana Faber Cancer Institute, Boston, Massachusetts 02115, USA.
Chi-Wei
CW
Lu
Akiko
A
Yabuuchi
Lingyi
L
Chen
Srinivas
S
Viswanathan
Kitai
K
Kim
George Q
GQ
Daley
D000818:Animals; D001755:Blastocyst / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002678:Chimera / Q000196:embryology; D004475:Ectoderm / Q000196:embryology*; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000502:physiology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D011247:Pregnancy; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D002070:Butadienes; D005419:Flavonoids; D009570:Nitriles; C113580:U 0126; D020929:Mitogen-Activated Protein Kinase Kinases; D016283:Proto-Oncogene Proteins p21(ras); C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one