Vertebrate Limb Regeneration and the Origin of Limb Stem Cells

David M. Gardiner, Tetsuya Endo, Mathieu Rondet and Susan V. Bryant

Developmental Biology Center and Department of Developmental and Cell Biology
University of California, Irvine, CA 92697

Urodele amphibians are unique among the vertebrates in the ability to regenerate their limbs as adults. In recent years, molecular analyses have begun to provide insights into the mechanisms controlling regeneration, and provide the opportunity to understand the remarkable regenerative abilities of urodeles. Numerous studies have demonstrated the critical role of connective tissue cells (collectively referred to as fibroblasts) in the control of growth and pattern formation during regeneration. Understanding the biology of this population of cells, in particular their response to the signals initiating and controlling regeneration, is critical to understanding how to devise strategies to stimulate regeneration in humans. Progress in this endeavor is being accelerated by progress in generating an EST database for regenerating axolotl limbs, and by advances in techniques for somatic cell transgenesis. We have begun to apply these technologies to the investigation of the cellular and molecular responses of dermal fibroblasts to the signals that initiate genesis of the regeneration blastema.