How do salamanders regenerate tissues, organs, and body parts, such as entire limbs? Conversely, why don’t mammals show comparable regenerative responses?

Our primary model organism for addressing these questions is an aquatic salamander, the red spotted newt. Newts possess the largest spectrum of regenerative abilities among adult vertebrates. During the past decade our laboratory has developed a number of methods, which had made these outstanding questions experimentally tangible. We place our findings on newt regeneration into an evolutionary context, and test our results in a variety of mammalian in vivo and in vitro assays.

We have two main experimental systems: Brain and limb regeneration.

1. Brain regeneration

In these projects we ask how the adult brain maintains its capacity to functionally replace lost neurons. We aim to identify cellular source(s) of new neurons, and to characterize molecular mechanisms controlling adult neurogenesis. In particular we are interested in how the brain senses the extent of cell loss in relation to the normal homeostatic state. A key current hypothesis of ours is that neurotransmitter signaling plays a central role in the control of neurogenesis both during homeostatic conditions and during regeneration. We study neurotransmitter signaling not only to reveal its impact on the production of new neurons but we also manipulate neurotransmitter signaling as a means to address lineage relationships between neural stem and progenitor cells in the adult brain.

2. Limb regeneration

The target tissue of our investigations in the context of limb regeneration is skeletal muscle. Skeletal muscle may contribute to limb regeneration in two ways; either by activation of quiescent stem cells or by dedifferentiation of differentiated muscle fibers. By various cell tracking strategies we try to compare these two processes to each other in terms of their relative contribution to the limb. We also characterize molecular processes involved in the generation of limb progenitors from skeletal muscle. At present we heavily focus on the balance between cell death andcell survival during the production of muscle progeny.