During embryological development signaling systems determine organization of the cells in the organism. One of these signals is the family of WNT proteins that activates Frizzled (FZD) receptors. This signaling system is crucial for proper embryogenesis and disturbances can lead to developmental defects and disease, such as cancer. Here, we propose to study the initial and proximal intracellular effects downstream of FZD activation, that involve intracellular players as dishevelled, beta-arrestin and heterotrimeric G proteins, in
order to better understand the basic signaling mechanisms employed by this signaling system. We hope that our results will improve understanding of development and disease and might lead to the discovery of novel targets for therapeutical intervention. E g the mechanistic results will be merged with ongoing projects in the different labaratories providing a physiological context such as developmental biology, sensory neuron physiology and cancer biology. Collaboration between the three applicants will lead to a synergistic effect for adressing technical, methodological and conceptional problems. Furthermore, exchange and education of people on various levels will promote exchange of expertise, knowledge and methodology. As a consequence, science and education are promoted and will benefit from the proposed collaborative project over borders.