Mescher Lab (retired)
Research Interests Developmental Biology; Regenerative Growth
We are interested in the tissue interactions during development which affect cell proliferation and growth. The focus of most of our work is the regenerating amphibian limb, which is able to reproduce itself completely following amputation. Growth and tissue regeneration in this system are dependent on an effect of the nerves, but the nature of the neural factor(s) which stimulate cell proliferation is not known. Peripheral nerves contain large amounts of transferrin, an iron-transport protein found in plasma which has been shown to be required for cell division. We have tested the hypothesis that nerves release transferrin and that this helps mediate the neural stimulation of proliferation in the regenerating amphibian limb (Dinsmore and Mescher, 1998). Using cultured tissues from regenerating limbs, we have shown that transferrin promotes cell proliferation as effectively as extracts of neural tissue, and with similar dosage effects. Using antibodies against amphibian transferrin, we developed a very sensitive enzyme-linked immunoassay (ELISA) for the factor and showed that transferrin is transported axonally in sciatic nerves and released from the ends of regenerating axons (Kiffmeyer et al., 1991). Work to date strongly supports the view that release of trophic factors such as transferring from regenerating axons forms an important basis for the growth-supporting role of nerves in limb regeneration (Mescher et al., 1997; Dinsmore and Mescher, 1998). Related work on cell cycling and apoptosis in cells of denervated blastemas extends this view of the neural effect on regeneration (Mescher et al., 2000).
In addition to the investigations on the role of nerves in regeneration, more recent studies in collaboration with colleagues in the Indiana University Center for Regenerative Biology and Medicine have identified genes important for limb regeneration (King et al., 2003). Our identification of immune-related genes in this project has led us to a novel approach to the study of regeneration involving the role of immune cells in this process. Our ideas in this area and the initial hypotheses to be tested are summarized in Harty et al. (2003).
These projects on the control of regenerative growth offer graduate students the opportunity to learn and gain experience with a variety of experimental methods, including microscopy, cell and organ culture, immunochemistry, as well as gene cloning and other basic molecular techniques
Indiana University School of Medicine