Journal
DEVELOPMENT GROWTH & DIFFERENTIATION
Volume 52, Issue 8, Pages 715-724Publisher
WILEY
DOI: 10.1111/j.1440-169X.2010.01208.x
Keywords
axolotl; blastema; limb regeneration; matrix metalloproteinase; wound epithelium
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Funding
- Defense Advance Research Projects Agency
- National Science Foundation through Ambystoma Genetic Stock Center at the University of Kentucky, Lexington
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Urodele amphibians (salamanders) are unique among adult vertebrates in their ability to regenerate structurally complete and fully functional limbs. Regeneration is a stepwise process that requires interactions between keratinocytes, nerves and fibroblasts. The formation of a wound epithelium covering the amputation site is an early and necessary event in the process but the molecular mechanisms that underlie the role of the wound epithelium in regeneration remain unclear. We have developed an ex vivo model that recapitulates many features of in vivo wound healing. The model comprises a circular explant of axolotl (Ambystoma mexicanum) limb skin with a central circular, full thickness wound. Re-epithelialization of the wound area is rapid (typically < 11 h) and is dependent on metalloproteinase activity. The ex vivo wound epithelium is viable, responds to neuronal signals and is able to participate in ectopic blastema formation and limb regeneration. This ex vivo model provides a reproducible and tractable system in which to study the cellular and molecular events that underlie wound healing and regeneration.
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