Determining the Molecular Basis for Cellular Dedifferentiation During Newt Limb Regeneration

Donald L. Atkinson, Vladimir Vinarsky, Tamara J. Stevenson, and Shannon J. Odelberg

Departments of Internal Medicine and Neurobiology and Anatomy
University of Utah, Salt Lake City, Utah

The initial stages of newt limb regeneration are characterized by the formation of a wound epithelium/apical epithelial cap and the dedifferentiation of a variety of cell types in the limb stump. The proliferation of these dedifferentiated cells produces a regeneration blastema, which is comprised of multipotent and/or progenitor cells that will later redifferentiate to form the specialized cells of the regenerated limb. We have previously shown that a factor or set of factors present in the regenerating newt limb, but absent in the nonregenerating limb, can induce the dedifferentiation of both newt and mouse myotubes (McGann et al, 2001, Proc. Natl. Acad. Sci. 98, 13699-13704). In an effort to identify the factor(s) that control this reversal of the differentiated state, we have performed a differential display analysis between regenerating and nonregenerating limbs and have identified several candidate dedifferentiation genes that are upregulated soon after limb amputation. Both in vitro and in vivo assays are being performed to elucidate the biochemical, cellular, and biological function of these genes during the initial stages of limb regeneration.