At approximately E5.5, the DVE (green) becomes evident at the distal tip of the epiblast concomitantly with the appearance of Wnt3 expression (blue) in the posterior visceral endoderm. At ~E5.75-E6.0, Wnt3 emanating from the posterior visceral endoderm (yellow arrows) activates its own expression and that of other markers of the primitive streak, such as T (striped), in the adjacent epiblast. The antagonistic activity of the AVE prevents the spread of Wnt3 activity in the anterior epiblast. In Wnt3-VE mutants, expression of primitive streak markers is delayed appearing at late E6.5 stages. In Cripto mutants, the AVE remains at the tip of the epiblast; this allows expansion of Wnt3 expression to the anterior visceral endoderm leading to radialization of the primitive streak. The black arrows indicate potential signaling events derived from extra-embryonic ectoderm and/or posterior visceral endoderm that may work in concert with Wnt3 in the establishment of the primitive streak and maintenance of gastrulation. Abbreviations: DVE, distal visceral endoderm stage; PS, Pre-streak stage; ES, early streak stage.