A biochemical pathway of secreted proteins that regulate D-V patterning in Xenopus. Black arrows indicate direct protein–protein interactions, blue arrows transcriptional regulation, and red arrows the flux of Chordin/BMP complexes toward the ventral side of the frog gastrula. (A) The dorsal center secretes Chordin (Chd), a BMP antagonist that binds BMP2/4/7 and ADMP, and transports them to the ventral side. The transport and release of BMPs is regulated by tolloid proteases (Xlr/BMP1), in cooperation with the scaffold protein Ont1, and inhibited by Sizzled (Szl). The ventral center secretes CV2, a protein that can inhibit BMPs at high doses, but also promote the flow of Chd/BMP complexes by concentrating them on the ventral side. BAMBI and Twisted gastrulation (Tsg) have been omitted for simplicity. (B) Opposite transcriptional regulation of dorsal and ventral centers by BMP signaling. BMP receptors (BMPR) phosphorylate SMAD1/5/8, repressing dorsal genes (Chd, ADMP, BMP2, and Ont1) and activating ventral genes (BMP2/4/7, CV2, Szl, Xlr). This network enables the D-V morphogenetic field to self-regulate by adjusting levels of BMP signaling on the dorsal and ventral side: At low BMP levels, ADMP and Ont1 are up-regulated, increasing BMP signaling and Chd degradation; at high BMP levels, CV2 and Szl are up-regulated, inhibiting BMPs and stabilizing Chd.
