"Tissue geometry as an emergent driver of collective cell migration"
The coordinated migration of multiple cells in a tissue is critical to a variety of biological processes, such as wound healing, cancer invasion, and morphogenesis. During vertebrate gastrulation, a migratory population of mesoderm and endoderm, collectively referred to as mesendoderm, migrates across the fibronectin-rich blastocoel roof (BCR) of the embryo. Leading-edge mesendoderm cells exhibit polarized protrusive behaviors, integrin-mediated tractions and directional migration along the BCR. Leading row traction forces are balanced by c-cadherin dependent cell-cell adhesions, which are required to pull follower row cells forward. Studies of collective cell migration in gastrulation have focused in large part on tissue explants removed from Xenopus laevis embryos. However, some cell behaviors (e.g., migration speed) change when the tissues are removed from the embryo and placed in vitro, confounding efforts to understand mechanisms of cell migration and tissue formation. To help address these limitations we are developing in silico approaches. We have constructed an agent based model (ABM) in the Cellular-Potts framework to investigate collective cell migration in the Xenopus embryo. Our model consists of 9 rules governing leader and follower cell dynamics and represents a biological dorsal marginal zone (DMZ) explant of 64 cells with both leader and follower cell agents over a 2 hour timecourse. Our model was calibrated to reproduce published experiments demonstrating mechanical properties of anisotropic tension in the DMZ explant. Model predictions suggests that cell intercalation and in vivo geometry contribute to increased collective cell migration speed during mesendoderm mantle closure along the BCR during gastrulation.
Additional authors: Gustavo Pacheco; Bette Dzamba; David R Shook; T.J. Sego; James A. Glazier; Shayn Peirce-Cottler; Douglas DeSimone