Neurotrophic regulation of fibroblast dedifferentiation during limb skeletal regeneration in the axolotl (Ambystoma mexicanum)

Akira Sato, Gillian M C Cummings, Susan V. Bryant, David M. Gardiner

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The ability of animals to repair tissue damage is widespread and impressive. Among tissues, the repair and remodeling of bone occurs during growth and in response to injury; however, loss of bone above a threshold amount is not regenerated, resulting in a "critical-size defect" (CSD). The development of therapies to replace or regenerate a CSD is a major focus of research in regenerative medicine and tissue engineering. Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues perfectly, yet like mammals do not regenerate a CSD. We report on an experimental model for the regeneration of a CSD in the axolotl (the Excisional Regeneration Model) that allows for the identification of signals to induce fibroblast dedifferentiation and skeletal regeneration. This regenerative response is mediated in part by BMP signaling, as is the case in mammals; however, a complete regenerative response requires the induction of a population of undifferentiated, regeneration-competent cells. These cells can be induced by signaling from limb amputation to generate blastema cells that can be grafted to the wound, as well as by signaling from a nerve and a wound epithelium to induce blastema cells from fibroblasts within the wound environment.

Original languageEnglish
Pages (from-to)444-457
Number of pages14
JournalDevelopmental Biology
Volume337
Issue number2
DOIs
Publication statusPublished - Jan 15 2010
Externally publishedYes

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Keywords

  • Axolotl
  • BMP
  • Cartilage
  • Dedifferentiation
  • Fibroblast
  • Limb
  • Neurotrophic factor
  • Regeneration

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

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