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D. Dormann, Xuesong Yang, Bakhtier Vasiev, Cornelis J Weijer Embryonic development is 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 and repellents. We investigate the molecular mechanisms by which cells signal each other during development, by which the 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 multicellular development, caused by the aggregation of thousands of individual amoebae, and during gastrulation in the chick embryo. In Dictyostelium we study the following questions: how is the movement behaviour of tens of thousands of individual amoebae coordinated by propagating waves of the diffusible secreted chemo-attractant, cyclic AMP to result in slug and fruiting body formation? I will discuss the molecular mechanisms that underlie cAMP wave generation and propagation, the mechanisms by which cells detect these dynamics gradients of cAMP, and translate this information in cell polarization and directed motion. Furthermore I will describe how modeling of these cell populations as complex excitable fluids have given insight in the question how the signaling system and cell movement interact to result in three dimensional multicellular morphogenesis. We have started to investigate the movement patterns underlying the primitive streak in the chick embryo and shown that this involves large scale highly coordinated cell flow patterns in the epiblast, the epithelial layer that will give rise to the embryo proper. We will outline our ideas and first results for the development of a hybrid cellular automata/continuous computational model that that should help us to understand the formation of the primitive streak during early chick development. We found strong evidence for an important role of chemotactic cell movement, in response to growth factor signals as an important mechanism responsible for the attractive and repulsive guidance of the mesoderm cells after their ingression through the primitive streak. The development of these models is expected to focus our further experiments on testing of plausible mechanisms underlying these complex developmental events. |
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