Dr Yelena Bernadskaya

Embryonic morphogenesis involves a wide array of cell migratory events. To understand this complex process we have combined confocal microscopy, genetic perturbations, and computational modeling to generate models of collective cell movement based on the observed in vivo behavior of migrating cardiopharyngeal cells (Trunk Ventral Cells, TVCs) in the basal chordate Ciona robusta. These cells migrate as polarized bilateral pairs, which consist of a committed leader and trailer, from the embryonic tail to the ventral trunk and constitute the simplest model of collective cell migration. Our model faithfully reproduces the evolution of migratory cell shape based on modulation of adhesive/protrusive forces acting within. We validate the predictions generated by the model in vivo by decreasing cell adhesion through expression of dominant negative Intb1 or increasing the protrusive activity of one cell using constitutively active RhoD/F and find that these perturbations can promote leader or trailer cell states in accordance with the model. Further, we find that Ddr and Intb1, two collagen-binding receptors we have shown to promote TVC polarity, have distinct roles in promoting adhesion by regulating distribution of focal adhesions and myosin in the migrating cell pair. Our model also predicts that migration of cell pairs is more efficient than migration of single cells and polarization along the direction of migration is preferable to side-by-side migration due to interaction of migrating cells with surrounding tissues. In vivo observations support this finding by showing that migration of single TVCs is less efficient than that of cell pairs. We thus gain insights into the basic rules governing collective cell migration in the context of live embryos by integrating biological observations with modeling. This work is funded by NIH/NIGMS R01 GM09603 award to LC and NIH F32 GM108369–01A1 to YB.