Fig. 8. Model of Eomes action in gastrulation. (A) At pregastrula stages, Eomes and Nodal expression are restricted to the ExE and epiblast (Epi), respectively. Nodal signalling is required first to induce formation of the DVE, which requires elevated Nodal signalling-levels for migration to the anterior side. A positive-feedback loop between Eomes in the ExE and Nodal in the epiblast is necessary to maintain high Nodal signalling thresholds required for DVE migration. Although Nodal signalling may directly regulate Eomes in the ExE, the requirement for Eomes in maintaining Nodal levels may be indirect possibly via regulation of levels of pro-protein convertases Furin and/or SPC4 in the ExE. (B) During gastrulation, Eomes expression is initiated in the posterior proximal epiblast and the PS, where it overlaps with Nodal. Eomes participates in the transcriptional control of E-cadherin downregulation, essential for cells to traverse the PS and delaminate as mesoderm and endoderm. Additionally, Eomes is required to specify the DE lineage and acts cooperatively with Nodal signalling to activate target genes responsible for APS specification.