Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

PLoS Comput Biol. 2020 Jun 24;16(6):e1007417. doi: 10.1371/journal.pcbi.1007417. eCollection 2020 Jun.

Abstract

During embryogenesis, morphogens form a concentration gradient in responsive tissue, which is then translated into a spatial cellular pattern. The mechanisms by which morphogens spread through a tissue to establish such a morphogenetic field remain elusive. Here, we investigate by mutually complementary simulations and in vivo experiments how Wnt morphogen transport by cytonemes differs from typically assumed diffusion-based transport for patterning of highly dynamic tissue such as the neural plate in zebrafish. Stochasticity strongly influences fate acquisition at the single cell level and results in fluctuating boundaries between pattern regions. Stable patterning can be achieved by sorting through concentration dependent cell migration and apoptosis, independent of the morphogen transport mechanism. We show that Wnt transport by cytonemes achieves distinct Wnt thresholds for the brain primordia earlier compared with diffusion-based transport. We conclude that a cytoneme-mediated morphogen transport together with directed cell sorting is a potentially favored mechanism to establish morphogen gradients in rapidly expanding developmental systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Body Patterning / physiology*
  • Brain / embryology
  • Cell Lineage
  • Cell Movement
  • Computational Biology
  • Computer Simulation
  • Embryonic Development
  • Gene Expression Regulation, Developmental*
  • Neural Crest / embryology
  • Neural Plate / embryology
  • Protein Transport
  • Signal Transduction
  • Software
  • Stochastic Processes
  • Vertebrates / embryology*
  • Wnt Proteins / physiology*
  • Zebrafish / embryology
  • beta Catenin / physiology

Substances

  • Wnt Proteins
  • beta Catenin