Junior Research Group: The role of Wnt signaling pathways in the regulation of progenitor function during embryonic development and organ regeneration

Junior research group leader: Dr. G. Weidinger

Previous and current research
We are interested in understanding the in vivo functions of the Wnt signaling network in embryonic development, stem cell maintenance and organ regeneration. During embryonic development, most organisms rely heavily on cell-cell communications to coordinate cell fate determination, cell proliferation, cell movement and to organize cells into tissues and organs. Signaling by the Wnt family of secreted proteins plays crucial roles in many of these processes. Recently, Wnt signaling pathways have also been implicated in the regulation of stem cell function in adults. Although Wnt signaling is known to be important at many stages of embryonic development, surprisingly little is known about the mechanisms of its action in many processes.

To be able to study the function of Wnt signaling at later stages of development and in adults, we have created transgenic zebrafish lines that allow us to inducibly activate and inhibit Wnt signaling. Using these tools we have begun to investigate the in vivo function of Wnt signaling in maintenance of stem cells and in organ regeneration.

Regeneration is a fascinating, but poorly understood process by which adult organisms can restore a limb or organ after injury. While mammals including humans have a very limited regenerative capacity, lower vertebrates, in particular salamanders and teleost fish, can regenerate a remarkable number of organs, including heart, retina, spinal cord, and limbs/fins. Many regenerative processes are thought to involve de-differentiation of differentiated cells into a stem cell population that gives rise to the regenerating tissues. The extracellular signals and the cell-biological mechanisms regulating this remarkable cellular plasticity are incompletely understood. Improved understanding of these processes holds great promise for regenerative medicine, since it will aid us in designing strategies to improve human tissue repair and regeneration.

Using our transgenic fish we have found that Wnt signaling is required for regeneration of fins in zebrafish, and is active during heart regeneration. We found that Wnt/beta-catenin signaling regulates formation and proliferation of the blastema, a population of stem cell-like progenitor cells that gives rise to all cell types of the regenerating fin. Currently we are investigating the cellular mechanisms of Wnt function during fin regeneration and how it interacts with other extracellular signaling pathways.

Future goals

• Identify downstream target genes of Wnt/beta-catenin signaling in regenerative processes
• Characterize the role of beta-catenin independent Wnt signaling in regeneration
• Investigate possible roles for Wnt signaling in maintenance of neural stem cells in vivo