Nodal signalling in the epiblast patterns the early mouse embryo

Shortly after implantation the mouse embryo comprises three tissue layers. The founder tissue of the embryo proper, the epiblast, forms a radially sym metric cup of epithelial cells that grows in close apposition to the extra- embryonic ectoderm and the visceral endoderm. This simple cylindrical struc ture exhibits a distinct molecular pattern along its proximal-distal axis(1 ). The anterior-posterior axis of the embryo is positioned later by coordin ated cell movements that rotate the pre-existing proximal-distal axis(2-5). The transforming growth factor-beta family member Nodal is known to be req uired for formation of the anterior-posterior axis(6). Here we show that si gnals from the epiblast are responsible for the initiation of proximal-dist al polarity. Nodal acts to promote posterior cell fates in the epiblast and to maintain molecular pattern in the adjacent extra-embryonic ectoderm. Bo th of these functions are independent of Smad2. Moreover, Nodal signals fro m the epiblast also pattern the visceral endoderm by activating the Smad2-d ependent pathway required for specification of anterior identity in overlyi ng epiblast cells. Our experiments show that proximal-distal and subsequent anterior-posterior polarity of the pregastrulation embryo result from reci procal cell-cell interactions between the epiblast and the two extra-embryo nic tissues.