Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Unravelling the rules of multicellular migration during development with models and experiments.
Linus J Schumacher

Last modified: 2014-03-28

Abstract


We study the mechanisms underlying cell migration in the developing embryo, using a computational model developed in close collaboration with in vivo experiments in the chick cranial neural crest. Here, a stream of cells has to invade a target tissue and at the same time distribute along the migratory route. Cranial neural crest cells are known to seek out a chemoattractant (VEGF). However, the chemoattractant is uniformly produced. Our working hypothesis is that a chemotactic gradient is induced by the cells themselves through internalisation of chemoattractant. This is represented computationally within a hybrid model framework (discrete cells off-lattice, continuous chemoattractant) on a growing domain.

Previous work has indicated the need for two subpopulations of cells with different behaviours. The presence of these subpopulations was validated experimentally, both by gene profiling and by confirming model predictions for tissue transplantation experiments. Our focus is now to extend this modelling framework, incorporating realistic cell sensing and differences in cell cohesion recently observed experimentally. The goal is to identify critical cell behaviours that lead to robust multicellular neural crest migration. Together with our collaborators we plan experiments and then conduct them in parallel in vivo, in vitro and computationally. Experimental results parameterise and inform the simulations, which in turn help to interpret existing results and suggest new experiments. We repeat this cycle of hypothesis generation and testing iteratively with the aim of providing a framework generalizable to multicellular migration in different organisms.

Keywords


cell migration; developmental biology; hybrid model