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

Development. 2021 Jan 20;148(2):dev189944. doi: 10.1242/dev.189944.

Abstract

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.

Keywords: BMP pathway; Embryo development; Gene regulatory network; Logical model; Nodal pathway; Paracentrotus lividus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastula / metabolism
  • Body Patterning* / drug effects
  • Body Patterning* / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Cell Lineage / drug effects
  • Cell Lineage / genetics
  • Computer Simulation
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism*
  • Gene Expression Regulation, Developmental / drug effects
  • Glycoproteins / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Models, Biological
  • Morpholinos / pharmacology
  • Nodal Protein / metabolism
  • Paracentrotus / drug effects
  • Paracentrotus / embryology*
  • Paracentrotus / genetics
  • Phenotype
  • Probability
  • Signal Transduction* / drug effects
  • Signal Transduction* / genetics
  • Stochastic Processes
  • Transforming Growth Factor beta / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Morpholinos
  • Nodal Protein
  • Transforming Growth Factor beta
  • chordin