Fig. 9.

Models for axis induction signaling in chick and mouse. (a) In the chick blastoderm (left panel, top/dorsal view, ~stage X, Eyal-Giladi and Kochav 1976) the outer marginal zone of the epiblast expresses Wnt8a in a posterior-to-anterior gradient (purple shading). In the PMZ, Pitx2 (yellow) activates Gdf1 expression (green). Subsequently (middle panel), the newly formed hypoblast (below the plane of the page) begins anterior migration and Gdf1 + Wnt8a cooperate to induce Lef1 in the PMZ and Nodal in the adjacent epiblast. Gata2 is expressed in the anterior marginal zone and antagonizes Gdf1 long-range. Nodal (magenta) is antagonized by Cerberus (Cer), which is expressed in the hypoblast. By the initial primitive streak stage (right panel, stage 2+, Hamburger and Hamilton 1951), the anterior migration of the hypoblast and migration of the endoblast beneath the posterior epiblast removes the inhibition of Nodal and allows feed-forward signaling leading to primitive streak formation. The same signaling molecules are ex-pressed in the primitive streak and induce organizer genes in Hensen’s node (dotted circle, Gsc, Chrd) at the anterior tip of the streak. (b) In the mouse, the earliest asymmetries are the expression of Lefty1 and Cerl (red-brown) at the tip of the postimplantation AVE (left panel, ~E5.0). These genes are regulated by Nodal (green) and Tdgf1, and Tdgf1 is regulated by beta-catenin in the absence of secreted Wnt ligand activity (stop symbol). Lefty1 and Cerl antagonize Nodal and feedback regulation drives AVE migration towards the proximal egg cylinder on one side (right panel, ~E5.5). Nodal activity is restricted to the posterior epiblast and is responsible for Wnt3 expression (blue), which in turn maintains Nodal. These signals cooperate to induce the primitive streak, which induces Hensen’s node toward the distal tip later in gastrulation. a anterior, p posterior, ExE extraembryonic ectoderm, VE visceral endoderm, ParE parietal endoderm