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Wnt signaling pathways – key for cellular communication in animals and humans

The formation as well as functional maintenance of all multicellular organisms requires that their cells constantly communicate with each other. Such cellular communication also allows cells to respond to a multitude of external signals. The communication between the cells takes place at the molecular level, with cells constantly exchanging signaling molecules. Examples of such signaling molecules can be genetically encoded proteins that control important cellular functions such as cell division and cell differentiation. These can act locally within tissues or may be transported over long distances in the organism and play a key role in the communication of cells in animals. Such proteins act like growth factors and can be released from specific groups of cells termed signaling centers.

Wnt proteins play a diverse and central role in cellular communication. They act as “ligands” that bind to receptors located on the cell surface (cell membrane). Upon engagement with a Wnt protein, these receptors transmit a signal through the membrane to the inside of the cell, where other proteins first pick up the activation signal and then relay it via other target proteins within the cell. These target proteins can influence the functionality of cells (e.g., adhesion, shape, motility) or, in interaction with other proteins in the cell nucleus, lead to activation/deactivation of specific genes. Cell behaviors are thereby controlled in specific ways, depending on which Wnt pathway is activated.

The various Wnt signaling pathways play fundamental roles in embryonic development, regulated growth, stem cell homeostasis, and cell differentiation. Ultimately, they ensure that an embryo develops into an intact, fully functioning organism. Disturbances in the Wnt signaling pathway at any level of signal processing and transmission can lead to diseases such as cancer.

In the Collaborative Research Center 1324, which is funded by the German Research Foundation (DFG), we work as an interdisciplinary consortium of scientists to investigate the mechanisms and functions of the Wnt signaling pathway. Our aim is to find out how cells communicate to ensure normal development of organisms and to understand the role of cellular signaling in human diseases.

The importance of Wnt signaling in disease research

Cell to cell communication ensures that cells can differentiate and tissue can regenerate. It becomes problematic for the body when this communication network fails to work as intended: disrupted signal transmission between cells can lead to developmental disorders, metabolic diseases or tumor formation. The human intestine is a prime example for the importance of targeted fine-tuning of the Wnt signaling pathway. The intestinal mucosa undergoes a cycle of constant cellular regeneration, in which the cells of the intestinal mucosa constantly die off and must be renewed. The Wnt signaling pathway plays an important role in this process.

Both reduction and overactivation of Wnt signaling can result from mutations in genes encoding components of Wnt signaling. As a consequence of overactivation, cells can multiply unhindered, leading to the development of cancer. The correct, regulated balance of Wnt signaling is therefore crucial for the organism.

In the Collaborative Research Center 1324, our goal is to achieve a deeper understanding of how the Wnt signaling network functions in a healthy organism and how disrupted signal transmission leads to complications. We are particularly interested in the role of Wnt signaling during embryonic development, carcinogenesis and their functions in stem cells. Our collaborative research center thus lays the foundation for biomedical progress.

Goals of the Collaborative Research Center 1324

We are in the unique position that many research groups in the region around Heidelberg are working on Wnt signaling. In our interdisciplinary network we have researchers in the fields of cell biology, structural biology, molecular biology, biophysics, mathematics and medicine who work together to understand the basic functions and mechanisms of the Wnt signaling pathway. In the first funding period, the Collaborative Research Center 1324 has set itself the goal of investigating the Wnt signaling pathway at the molecular level. Using model organisms such as hydra, fruit flies, fish, frogs and mice, but also using human cells and tissues, we work together to achieve our goals.

In the first funding period we primarily focused on how Wnt signaling pathways function with respect to their cellular environment. Now, in the second funding period, we will focus more on investigating the spatial and temporal control of the signaling pathways and their cellular dynamics. Specifically, the SFB 1324 works on questions related to the secretion of Wnt proteins from cells and their interaction with receptors.

Furthermore, we investigate how the Wnt signaling pathway integrates with other downstream signaling pathways, how dynamically the Wnt signaling pathway acts in cells and what consequences this has for the organism. In the Collaborative Research Center, scientists from Heidelberg University work closely with their medical faculties in Heidelberg and Mannheim, the German Cancer Research Center (DKFZ), the European Laboratory for Molecular Biology (EMBL), the Karlsruhe Institute of Technology (KIT) and the University of Göttingen.