How and at what stage of development are the axes of the body determined? The left-right axis of the mouse embryo is generated de novo at embryonic day (E) 8.0 in a manner dependent on pre-existing positional cues. The anterior-posterior (A-P) axis becomes apparent earlier when distally located visceral endoderm migrates toward the future anterior side at E5.5. The direction of this migration is predetermined by asymmetric expression of Lefty1 and Cerl1(Cerberus-like 1). Asymmetric expression of Lefty1 takes place even earlier, in the primitive endoderm of the implanting blastocyst, pushing back the origin of the A-P axis to the peri-implantation stage. Although its functional significance remains to be seen, studies on how this molecular asymmetry emerges may provide insight into the origin of A-P polarity. The first cell fate decision occurs by the morula stage. Although blastomeres at the two-cell or four-cell stage may have biased fates, it is currently unknown whether this bias has any causal relation to later fate.