Fig. 5.

The gene regulatory network linkages that coordinate Delta-Notch signaling with the wnt8-blimp1 expanding-torus subcircuit. (A) Fate map and summary network subcircuit showing all linkages. Expression of delta is dominantly repressed by HesC and activated by the factor Runx, whereas hesC is activated broadly, amplified by receiving a cis-regulatory Delta-Notch signal input and repressed by Blimp1. For clarity the Wnt signaling pathway is simplified to show only the end result, nuclearized β-catenin interacting with the transcription factor Tcf (nb-Tcf); NICD, Notch intracellular domain; chevron, intercellular input. Fate map at left shows the future skeletal mesoderm (SM), purple; NSM, green; and endoderm, brown. (B–D) Depiction of linkages that are active in given stages and domains (i.e., views from the nuclei, VFNs). Note that NSM cells migrate toward vegetal pole as a consequence of skeletogenic cell ingression, and thus cells marked green in (B) and (C) are of the same lineage. Components shown in gray are inactive, and in color are active. (B) VFN for eighth cleavage NSM precursors. The blimp1/wnt8 subcircuit is active, whereas delta is not transcribed due to the presence of the dominant-acting HesC repressor. (C) VFN for NSM at early mesenchyme blastula. Expression of delta expression begins as hesC transcription ceases due to repression by Blimp1. Also due to Blimp1 repression, the blimp1/wnt8 subcircuit has been extinguished. The onset of delta expression in the NSMs is thereby synchronized with the disappearance of wnt8 from those same cells in the center of the moving torus. (D) VFN for endoderm at early mesenchyme blastula. The blimp1/wnt8 subcircuit is now active as a result of previous Wnt8 diffusion from the NSM (18). Delta-Notch signaling occurs in response to the NSM Delta ligand, further enhanced by transcription of the Notch receptor, which in this domain is not subject to Blimp1 repression; however, delta expression is reciprocally forbidden by Notch-driven HesC expression.