Chemotactic cell movement a key mechanism of tissue dynamics and morphogenesis

Abstract

We investigate the molecular mechanisms by which cells produce and detect chemotactic signals and translate this information in directed movement up or down chemical gradients in the social amoebae Dictyostelium discoideum, and during gastrulation in the chick embryo. Investigation of Dictyostelium mutants with changes in cAMP cell-cell signalling dynamics and chemotaxis, show how cellular heterogeneity in signalling dynamics and polarised activation of the actin-myosin cytoskeleton drive aggregation, cell sorting, slug formation and migration. Our experiments furthermore show that chemotactic cell movement plays a critical role during gastrulation in the chick embryo. We suggest that epiblast cell movement during the formation of the primitive streak as well as the movement of the mesoderm cells after their ingression through the streak is controlled by a combination of attractive and repulsive guidance cues. We have identified FGF4 and VEGFA as attractive cues for mesoderm cells, while FGF8 and Wnt's act as repulsive signals. We are currently establishing how signalling and movement interact and use models to design experimentally testable hypotheses.