Development. 2020 Dec 9;dev.189944. doi: 10.1242/dev.189944. Online ahead of print.
Swann Floc’hlay 1, Maria Dolores Molina 2, Céline Hernandez 1, Emmanuel Haillot 2, Morgane Thomas-Chollier 1 3, Thierry Lepage 4, Denis Thieffry 5
Affiliations
1 Institut de Biologie de l’ENS (IBENS), École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France.
2 Institut Biologie Valrose, Université Côte d’Azur, Nice, France.
3 Institut Universitaire de France (IUF), 75005 Paris, France.
4 Institut Biologie Valrose, Université Côte d’Azur, Nice, France denis.thieffry@ens.psl.eu tlepage@unice.fr.
5 Institut de Biologie de l’ENS (IBENS), École Normale Supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France denis.thieffry@ens.psl.eu tlepage@unice.fr.
Abstract
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 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, reveals a dominance of the BMP pathway over the Nodal pathway, and stresses the crucial impact of the rate of Smad activation in D/V 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.
PMID: 33298464
DOI: 10.1242/dev.189944