Embryonic development is critically dependent on a number of distinct cellular behaviours such as cell division and cell death, cell differentiation and cell movement, which all have to be precisely controlled in space and time. In many cases cell movement is controlled by diffusible chemical signals that act as chemo-attractants or repellents. We investigate the molecular mechanisms by which cells signal each other during development, how cells detect these signals and how they translate this information in directed movement. We study these questions in two different experimental systems, in the social amoebae Dictyostelium discoideum, a simple genetically tractable micro-organism showing a relatively simple starvation induced multicellular development, where thousands of individual amoebae aggregate to form a fruiting body and during gastrulation in the chick embryo During Dictyostelium development the movement of tens of thousands of individual amoebae is coordinated by propagating waves of the diffusible secreted chemo-attractant, cyclic AMP. These cAMP waves direct the chemotactic aggregation of thousands of cells dispersed in the leaf litter of the soil towards an aggregation centre where they form a hemispherical aggregate. In the aggregate the cells differentiate into two cell types, prestalk and prespore cells, which continue to form a migratory slug. The slug migrates to the surface to form a fruiting body consisting out of a stalk supporting a mass of spores. The movement of the cells during all these stages of development is controlled by propagating cAMP waves. I will discuss the molecular mechanisms that underlie cAMP wave generation and propagation and the mechanisms by which cells detect these dynamics gradients of cAMP, and translate this information in cell polarization and directed motion. These investigations rely heavily on the use of mutants to characterize signaling pathways and advanced imaging methods to follow the dynamics of signaling pathways and resulting changes in the cytoskeleton in wildtype and mutant strains as well as mathematical modeling of the interactions between signal propagation and the resulting cell movement (Dormann and Weijer, 2003; Vasiev and Weijer, 2003). We have also started to explore control of cell movement during early vertebrate development, especially the control of migration of mesoderm cells during the early stages of gastrulation in the chick embryo. Mapping of the movement trajectories of cells expressing the green fluorescent protein during the early phases of gastrulation shows that the cells move very directed over long distances. The movement of mesoderm cells appears to be guided by both attractive and repulsive cues involving distinct members of the FGF and VEGF families of growth factors (Yang et al., 2002). Signal detection and gradient reading appears to involve the extension of long cellular processes to sense signals in the environment. We are now investigating the molecular mechanisms involved in detection and translation of these signals in directed movement using in-vivo imaging techniques.
University of Oxford (2004) J Physiol 561P, SA17
Research Symposium: CHEMOTACTIC CELL MOVEMENT AND ITS ROLE IN DEVELOPMENT
Weijer,Cornelis ;
1. Wellcome Trust Biocentre, University of Dundee, Dundee, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.