Fig. 5. A model of Churchill functions and regulation during early development in chick. (A-D) The embryologist's view, showing embryos at four stages, viewed obliquely from the dorsal side (posterior towards the right), with their germ layers teased apart (brown represents hypoblast, yellow the epiblast). (A) Stages XI-XII. The hypoblast emits FGF8, which induces the early pre-neural genes ERNI and SOX3 (orange) in the overlying epiblast (yellow). At this stage, cells in this domain are still uncommitted. Nodal is expressed in the posterior epiblast but is inhibited by Cerberus secreted by the hypoblast. (B) Stages XIII-2. The hypoblast is displaced from the posterior part of the embryo by the endoblast (white), which allows Nodal signalling, in synergy with FGF, to induce Brachyury (Bra) and Tbx6L and ingression (red arrows) to form the primitive streak (red, its position is outlined with a broken line in the epiblast layer). (C) Stages 3⁺-4. Continued FGF signalling now induces churchill in a domain of the epiblast (light blue). The border of the epiblast territory destined to ingress to form mesoderm is shown with a broken black line. (D) At the end of stage 4, churchill induces SIP1, which blocks Bra, Tbx6L and further ingression of epiblast into the anterior streak. The epiblast remaining outside the streak (blue) is now sensitized to neural-inducing signals emanating from the node (blue arrows). (E) The same model as a genetic cascade. Black represents interactions described by Sheng et al. (Sheng et al., 2003). Grey indicates other interactions from published data. The time axis (right) shows time in hours after a graft of Hensen's node, and the colour gradients indicate progressive commitment to epidermis (yellow), neural (blue) and mesoderm (red). BMP/Smad/Sip1 interactions regulate the epidermis-neural plate border, while ChCh/Sip1/FGF/Bra/Tbx6 regulate the mesoderm-neural decision. The asterisk indicates phosphorylated Smad1.??? represents as yet unknown components. Modified, with permission, from Sheng et al. (Sheng et al., 2003).