Gene expression patterns specific to the regenerating limb of the Mexican axolotl

James R. Monaghan, Antony Athippozhy, Ashley W. Seifert, Sri Putta, Arnold J. Stromberg, Malcolm Maden, David M. Gardiner, S. Randal Voss

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Salamander limb regeneration is dependent upon tissue interactions that are local to the amputation site. Communication among limb epidermis, peripheral nerves, and mesenchyme coordinate cell migration, cell proliferation, and tissue patterning to generate a blastema, which will form missing limb structures. An outstanding question is how cross-talk between these tissues gives rise to the regeneration blastema. To identify genes associated with epidermis-nervemesenchymal interactions during limb regeneration, we examined histological and transcriptional changes during the first week following injury in the wound epidermis and subjacent cells between three injury types; 1) a flank wound on the side of the animal that will not regenerate a limb, 2) a denervated limb that will not regenerate a limb, and 3) an innervated limb that will regenerate a limb. Early, histological and transcriptional changes were similar between the injury types, presumably because a common wound-healing program is employed across anatomical locations. However, some transcripts were enriched in limbs compared to the flank and are associated with vertebrate limb development. Many of these genes were activated before blastema outgrowth and expressed in specific tissue types including the epidermis, peripheral nerve, and mesenchyme. We also identified a relatively small group of transcripts that were more highly expressed in innervated limbs versus denervated limbs. These transcripts encode for proteins involved in myelination of peripheral nerves, epidermal cell function, and proliferation of mesenchymal cells. Overall, our study identifies limb-specific and nerve-dependent genes that are upstream of regenerative growth, and thus promising candidates for the regulation of blastema formation.

Original languageEnglish
Pages (from-to)937-948
Number of pages12
JournalBiology Open
Issue number10
StatePublished - Oct 15 2012

Bibliographical note

Funding Information:
The axolotls were obtained from the Ambystoma Genetic Stock Center at the University of Kentucky, which is funded by the National Science Foundation [DBI-0951484 to S.R.V.]. The Ambystoma GeneChip was generated under National Institute of Health [R24-RR016344 to S.R.V.] and Army Research Office [W911NF-09-1-0305 to S.R.V.]. The work was supported by National Institute of Health [RC2-NS069480 to S.R.V. and M.M.] and funding from The Regeneration Project at University of Florida to S.R.V., M.M., D.M.G., and J.R.M.

Publisher Copyright:
© 2012 Published by The Company of Biologists Ltd.


  • Axolotl
  • Limb
  • Regeneration
  • Wound healing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Agricultural and Biological Sciences (all)


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