Limb development and regeneration – How to Regenerate a New Leg: What we can learn from salamanders – Alone among vertebrates, urodele amphibians are able to regenerate lost body parts as adults. The key to this ability is that limb cells are triggered to dedifferentiate and reinitiate growth and pattern formation. Our strategy is to use axolotls (Ambystoma mexicanum) to discover the signals that trigger the regeneration response, in the belief that these signals have enormous potential and consequences for human health. Our long term goals are to identify the regeneration-enabling signals in limbs, in order to support progress towards the eventual application of these molecules to the improvement of human repair mechanisms. current research, we are using assays derived from the extensive experimental history of regenerating limbs, to test the roles of several signaling molecules known to be essential for limb development.
These assays are designed to examine the signals that initiate regeneration, those that are needed to establish a blastema, as well as those that are required for intercalary growth between the new limb tip and the amputation plane. In addition, we are taking a genomics approach to the isolation of genes needed for regeneration. A library of arrayed cDNAs made from limbs at different stages of regeneration will be screened with stage specific probes to identify genes expressed at different times in regeneration. We are especially interested in any novel factors that might be involved in transforming the differentiated limb stump into a blastema. The tools and knowledge are in place to attack complex systems, and understanding regeneration is likely to lead to new approaches and therapies for replacing or repairing lost, damaged or diseased parts of the body.
- Satoh, A., Cummings, GM., Bryant, SV., and Gardiner DM. (2010) Neurotrophic regulation of fibroblast dedifferentiation during limb skeletal regeneration in the axolotl (Ambystoma mexicanum). Developmental Biology, 337(2):444-57
- Holden, PK., Li, C., Da Costa, V., Sun, CH., Bryant, SV., Gardiner, DM., and Wong, BJ.(2009)The effects of laser irradiation of cartilage on chondrocyte gene expression and the collagen matrix. Lasers Surg Med, 41(7):487-91.
- Ghosh, S., Roy, S., Séguin, C., Bryant, SV., and Gardiner DM. (2008) Analysis of the expression and function of Wnt-5a and Wnt-5b in developing and regenerating axolotl (Ambystoma mexicanum) limbs. Dev Growth Differ., 50(4):289-97
- Satoh, A.,Bryant, SV., and Gardiner, DM. (2008) Regulation of dermal fibroblast dedifferentiation and redifferentiation during wound healing and limb regeneration in the Axolotl. Dev Growth Differ., 50(9):743-54
- Satoh, A., Gardiner, DM., Bryant, SV., and Endo, T. (2007) Nerve-induced ectopic limb blastemas in the Axolotl are equivalent to amputation-induced blastemas. Developmental Biology, 312(1):231-44
- Gardiner, D.M. and Susan V. Bryant (2006). Limb Regeneration. in “Fins into Limbs”, Brian Hall (ed.). Univ. Chicago Press. Chicago.
- Putta, S., Smith, J.J., Walker, J., Rondet, M., Weisrock, D.W., Monaghan, J., Samuels, A.K., Kump, K., King, D.C., Maness, N.J., Habermann, B., Tanaka, E., Bryant, S.V., Gardiner, D.M., Parichy, D.M. and Voss, S.R. (2004). From Biomedicine to Natural History Research: Expressed Sequence Tag Resources for Ambystomatid Salamanders. BMC Genomics 5:54-70.
- Endo, T., Bryant, S.V., and Gardiner, D.M. (2004). A stepwise model system for limb regeneration. (2004). Dev. Biol. 270:135-145.
- Bryant, S.V., Endo, T, and Gardiner, D.M.(2002) Vertebrate limb regeneration and the origin of limb stem cells. IJDB. 46:887-896
- Gardiner, D.M., Endo, T. and Bryant, S.V. (2002). The molecular basis of amphibian limb regeneration: Integrating the old with the new. Sem. Cell Dev. Biol. 13:345-352.