Mechanisms and functions of Wnt signaling

Wnt signaling pathways play a decisive role in development, cell differentiation, tumorigenesis and tumor progression. Wnt ligands are secreted, lipidated proteins that bind to half a dozen different receptors to activate multiple downstream signaling cascades. Wnt pathways relay signals from divergent ligand-receptor interactions to a network of downstream signaling of conserved cytoplasmic factors. Despite having gained an enormous amount of knowledge about components and mechanisms of Wnt signaling, we are now facing a multitude of new questions about the specificity of signaling input and the control of signaling output during development and in disease.

To advance our understanding of molecular mechanisms governing Wnt signal transduction, the Collaborative Research Center CRC1324 is structured into two major research areas: (A) Wnt secretion, trafficking and receptor-ligand interactions and (B) Wnt coupling to downstream and context-dependent signaling. In the first research area, we want to understand how Wnt ligands are produced, how they are modified and how they are transported in the extracellular space. We also want to unravel the Wnt ligand receptor interactions and understand how they specify the signaling response and induce different signaling cascades. In the second research area, we will focus on the molecular dynamics of the Wnt machinery to understand how different Wnt pathways elicit distinct biological responses and how Wnt signaling is coupled to different downstream factors. We also want to understand the spatio-temporal dynamics of Wnt signaling, i.e., how Wnt signaling regulates oscillations and wave patterns. To address these questions, we will combine a wide range of model systems including hydra, fly, fish, frog, as well as mouse and human cells with cutting-edge technologies including advanced fluorescence microscopy, genetic screens and genome engineering, and proteomics.

Because Wnt signaling is of crucial importance for so many biological processes and diseases, the overarching and long-term goal of the Collaborative Research Center CRC 1324 is to gain a mechanistic understanding of Wnt signaling and to investigate its physiological consequences in a representative spectrum of model systems.

 

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