In mammalian embryos, molecular cross-talk with extraembryonic tissues is essential to elaborate the primary body axes. Here, we review a series of reciprocal interactions that occur shortly after implantation in the uterus, and discuss how they are integrated in a complex signaling network to establish antero-posterior and dorso-ventral polarity. At the heart of this signaling network is the TGFbeta-related protein Nodal which acts on extraembryonic tissues to induce positive and negative feedback regulators at opposite poles of the egg cylinder. This likely results in an activity gradient which is instrumental to pattern the embryo proper.