The Department of Biomedicine

BBB Seminar: Gilbert Weidinger

Mechanisms of naturally occurring organ regeneration in the zebrafish

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Gilbert Weidinger
Institute for Biochemistry and Molecular Biology, Ulm University, Germany

While all organisms have evolved mechanisms to cope with tissue damage, lower vertebrates have much higher abilities to regenerate adult organs or appendages than mammals. In particular, fish and salamanders can fully regenerate fins and limbs, but also internal organs like the heart. The zebrafish is a great model in which to uncover the cellular and molecular mechanisms of naturally occurring regeneration, due to the possibility for us to perform genetic and transgenic manipulations.

An important question in regeneration research is whether cells that re-build the lost tissue are derived from stem cells or from differentiated adult cells. We have shown that differentiated osteoblasts are an important source of regenerating bone in the zebrafish fin. These cells de-differentiate, become migratory and proliferative, but they do not attain multipotency, but rather only form osteoblasts in the regenerated fin. Thus, de-differentiation of mature adult cells is an important cellular principle underlying regeneration.

De-differentiated cells form a mass of proliferative progenitor cells termed the blastema. During regenerative growth, proliferation and differentiation of blastema cells need to be tightly controlled and coordinated. We have uncovered roles of Notch and Wnt signaling in these processes. Intriguingly we find that Wnt/beta-catenin signaling does not directly regulate proliferation of cells in the regenerate, but rather sets up signaling centers within the blastema that send a number of secondary signals. Thus, Wnt/beta-catenin signaling appears to be a "master regulator" of regenerative growth since it defines organizers of regeneration.

Host: Donald Gullberg, Department of Biomedicine