A gene regulatory network controlling hhex transcription in the anterior endoderm of the organizer

►We determined how the Nodal, Wnt, and BMP pathways and their downstream transcription factors regulate hhex expression in the gastrula organizer. ►Nodal signaling directly activates hhex transcription via FoxH1/Smad2 sites in the proximal promoter. ►BMP targets Vent 1 and Vent2 repress hhex in the ventral tissue. ►Maternal Wnt cooperates with Nodal and indirectly activates hhex expression via Siamois and Twin. ►Siamois/Twin stimulate hhex transcription by inducing BMP-antagonists, which exclude Vents from the organizer allowing hhex transcription.