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 organiser 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 assembled 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 ventral ectoderm, ciliary band and dorsal ectoderm. Our model simulations further recapitulate various morphant phenotypes, reveal a dominance of the BMP pathway over the Nodal pathway and stress the crucial impact of the rate of Smad activation in dorsal-ventral patterning. These results emphasise the key role of the mutual antagonism between the Nodal and BMP2/4 pathways in driving early dorsal-ventral patterning of the sea urchin embryo.