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The Role of Nerve Signaling in Limb Genesis and Agenesis During Axolotl Limb Regeneration
Akira Satoh, PhD1; Michelle A. James, MD2; David M. Gardiner, PhD3
1 Okayama University, R.C.I.S., 3-1-1, Tsushima-naka, Okayama-city, Okayama, 700-8530, Japan
2 Department of Orthopedic Surgery, Shriners Hospital for Children, 2425 Stockton Boulevard, Sacramento, CA 95817-2215
3 Department of Developmental and Cell Biology and The Developmental Biology Center, Natural Sciences II Division, 4111 Natural Sciences II, University of California at Irvine, Irvine, CA 92697-2305. E-mail address: dmgardin@uci.edu
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Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Japan Society for the Promotion of Science and the Defense Advanced Research Projects Agency (DARPA), U.S. Department of Defense. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2009 Jul 01;91(Supplement 4):90-98. doi: 10.2106/JBJS.I.00159
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Vertebrate appendages such as limbs and fins share evolutionarily conserved mechanisms for development and regeneration, implying that they evolved from an appendage that arose on a common ancestor1. This conservation of developmental mechanisms is one of the fundamental discoveries of molecular genetics and is the basis for our emerging understanding of the evolution of animal genomes. The molecules involved in the signaling pathways that regulate limb development are not only conserved at the level of nucleotides and/or amino acids but also at the functional level, so that experimentally substituting homologous genes between species as divergent as humans and Drosophila can rescue the function of a mutant gene2. The fact that this remarkable degree of conservation has been maintained over the course of evolution implies that the mechanisms for appendage development have evolved once. Similarly, the mechanisms regulating limb regeneration are largely the same as those regulating limb development3,4, and thus evolution appears to have selected for a conserved set of signaling pathways that regulate both vertebrate limb development and regeneration.
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