Tony Mescher Lab

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

Selected Publications

Werner SR, Mescher AL, Neff AW, King MW, Chaturvedi S, Duffin KL, Harty MW, Smith RC. (2007) Neural MMP-28 expression precedes myelination during development and peripheral nerve repair.  Dev Dyn.  Sep 6; [Epub ahead of print]

Neff AW, King MW, Harty MW, Nguyen T, Calley J, Smith RC, Mescher AL. (2005) Expression of Xenopus XlSALL4 during limb development and regeneration.  Dev Dyn. 233(2):356-367

Mescher AL, Neff AW (2005). Regenerative capacity and the developing immune system. Adv. Biochemical Engineering/ Biotechnology 93: 39-66.

Mescher AL, Neff AW (2004). Loss of regenerative capacity: A trade-off for immune specificity?  Cellscience (on-line Cellscience.com/reviews2)

King, M.W., T. Nguyen, J. Calley, M.W. Harty, M.C. Muzinich, A.L. Mescher, C. Chalfant, M. N’Cho, K. McLeaster, J. McEntire, D. Stocum, R.C. Smith, and A.W. Neff. (2003) Identification of genes expressed during Xenopus laevis limb regeneration by using subtractive hybridization. Devel. Dynamics 226: 398-409.

Harty, M., A.W. Neff, M.W. King, and A.L. Mescher (2003) Regeneration or scarring: An immunologic perspective. Devel. Dynamics 226: 268-279.

Mescher, A.L., G. W. White, and J. J. Brokaw (2000) Apoptosis in regenerating and denervated, nonregenerating urodele forelimbs. Wound Repair and Regeneration 8: 100-116.

Rageh, M.A.E., L. Mendenhall, E.E.A. Moussad, S.E. Abbey, A.L. Mescher, and R.A. Tassava (2002) Vasculature in pre-blastema and nerve-dependent blastema stages of regenerating forelimbs of the adult newt, Notophthalmus viridescens. J. Experimental Zoology  292: 255-66.

Dinsmore, C.E. and Mescher, A.L. (1998) The role of the nervous system in regeneration.  In Cellular and Molecular Basis of Regeneration: From Invertebrates to Humans  P. Ferretti and J. Geraudie, eds.  John Wiley & Sons, Chichester. Pp. 79-108.

Mescher, A.L., Connell, E., Hsu, C., Patel, C. and Overton, B. (1997) Transferrin is necessary and sufficient for the neural effect on growth in amphibian limb regeneration blastemas.  Develop. Growth Differen.  39:677-684.

Mescher, A.L. (1996) The cellular basis of limb regeneration in urodeles.  Internat. J. Devel. Biol.  40:785-796.

Mescher, A.L. (1992) Trophic activity of regenerating peripheral nerves.  Comments Developmental Neurobiology  1:373-390.

Kiffmeyer, W.R., Tomusk E.V. and Mescher, A.L. (1991)  Axonal transport and release of transferrin in nerves of regenerating amphibian limbs.  Developmental Biology  147:392-402.