Fig. 3. Models of regulatory pathways for mesoderm induction. Depictions of embryos at pre-gastrulation stages. Domains of Nodal/Vg1 expression are indicated in blue; blue arrows indicate Nodal/Vg1 activity, orange arrows indicate Wnt/ß-catenin activity, and purple arrows correspond to the activity of other factors as noted. (A) In Xenopus (lateral view), zygotic Xnr transcripts (blue arrows) are activated by the maternally encoded VegT T-box transcription factor (purple arrow). Cortical rotation after fertilization leads to translocation of maternal dorsalizing signals and the stabilization of ß-catenin (orange arrow) on the dorsal side. The levels of Xnr as well as maternal Vg1 transcripts are higher dorsally (thicker blue arrows), and specify the dorsal-ventral patterning of the mesoderm in the marginal zone. (B) In zebrafish (lateral view), zygotic cyc and sqt transcripts (blue arrows) at the blastoderm margin are activated by an as yet unidentified signal(s) that emanates from the extraembryonic yolk syncytial layer. Graded Nodal signaling (thin and thick arrows) specifies the animal-vegetal patterning of mesoderm. (C) In the chick embryo (dorsal view), Vg1 (blue arrow) expressed at the posterior marginal zone cooperates with posteriorly-expressed Wnt8c (orange arrow) to induce streak formation in the adjacent epiblast. (D) In the mouse embryo (lateral view), Nodal proprotein (Nodal-Pp) expressed in the epiblast signals to the extraembryonic ectoderm, which activates expression of its proprotein convertases Furin and Pace4, as well as Bmp4. Production of the active mature Nodal ligand induces its positive autoregulatory loop (fast-acting; blue arrow), as well as a slower feedback loop (orange arrow) through Bmp4 and Wnt3; an additional feedback loop may take place through Cripto upregulation by Bmp4 and Wnt3 (Beck et al., 2002; Morkel et al., 2003).