Deciphering and modelling the TGF-β signalling interplays specifying the dorsal-ventral axis of the sea urchin embryo

During sea urchin development, secretion of Nodal and BMP2/4 ligands and their antagonists Lefty and Chordin from a ventral organizer region specifies the ventral and dorsal territories. This process relies on a complex interplay between the Nodal and BMP pathways through numerous regulatory circuits. To decipher the interplay between these pathways, we used a combination of treatments with recombinant Nodal and BMP2/4 proteins and a computational modelling approach. We further developed a logical model focusing on cell responses to signalling inputs along the dorsal-ventral axis, which was extended to cover ligand diffusion and enable multicellular simulations. Our model simulations accurately recapitulate gene expression in wild type embryos, accounting for the specification of the three main ectodermal regions, namely ventral ectoderm, ciliary band and dorsal ectoderm. Our model further recapitulates various mutant phenotypes. Temporal analysis revealed the dominance of the BMP pathway over the Nodal pathway, and suggested that the rate of Smad activation governs D/V patterning of the embryo. These results indicate that a mutual antagonism between the Nodal and BMP2/4 pathways is the fundamental mechanism driving early dorsal-ventral patterning.