The earliest cell fate decision in the mammalian embryo separates the extra
-embryonic trophoblast lineage, which forms the fetal portion of the placen
ta, from the embryonic cell lineages. The body plan of the embryo proper is
established only later at gastrulation, when the pluripotent epiblast give
s rise to the germ layers ectoderm, mesoderm and endoderm. Here we show tha
t the T-box gene Eomesodermin(1) performs essential functions in both troph
oblast development and gastrulation, Mouse embryos lacking Eomesodermin arr
est at the blastocyst stage. Mutant trophoectoderm does not differentiate i
nto trophoblast, indicating that Eomesodermin may be required for the devel
opment of trophoblast stem cells(2), In the embryo proper, Eomesodermin is
essential for mesoderm formation. Although the specification of the anterio
r-posterior axis and the initial response to mesoderm-inducing signals is i
ntact in mutant epiblasts, the prospective mesodermal cells are not recruit
ed into the primitive streak. Our results indicate that Eomesodermin define
s a conserved molecular pathway controlling the morphogenetic movements of
germ layer formation and has acquired a new function in mammals in the diff
erentiation of trophoblast.