Retinoic acid receptor regulation of epimorphic and homeostatic regeneration in the axolotl.

  • Professor
  • Associate Faculty, Spinal Cord and Brain Injury Research Center
  • Director, Ambystoma Genetic Stock Center
  • Bioinformatics and Computational Biology
  • Biology
  • Biology Education
  • Cell and Developmental Biology
  • Ecology and Evolutionary Biology
  • Genetics and Genomics
  • Neuroscience and Neurobiology
  • Pharmacology Toxicology and Environmental Health
  • Physiology
(859) 257-9888
TitleRetinoic acid receptor regulation of epimorphic and homeostatic regeneration in the axolotl.
Publication TypeJournal Article
Year of Publication2017
JournalDevelopment (Cambridge, England)
Date Published2017

Salamanders are capable of regenerating amputated limbs by generating a mass of lineage-restricted cells called a blastema. Blastemas only generate structures distal to their origin unless treated with retinoic acid (RA), which results in proximodistal (PD) limb duplications. Little is known about the transcriptional network that regulates PD duplication. In this study, we target specific retinoic acid receptors (RARs) to either PD duplicate (RA treatment or RARγ agonist) or truncate (RARβ antagonist) regenerating limbs. RARE-EGFP reporter axolotls showed divergent reporter activity in limbs undergoing PD duplication versus truncation, suggesting differences in patterning and skeletal regeneration. Transcriptomics identified expression patterns that explain PD duplication, including upregulation of proximal homeobox gene expression and silencing of distal-associated genes, whereas limb truncation was associated with disrupted skeletal differentiation. RARβ antagonism in uninjured limbs induced a loss of skeletal integrity leading to long bone regression and loss of skeletal turnover. Overall, mechanisms were identified that regulate the multifaceted roles of RARs in the salamander limb including regulation of skeletal patterning during epimorphic regeneration, skeletal tissue differentiation during regeneration, and homeostatic regeneration of intact limbs.

Short TitleDevelopment
Enter your linkblue username.
Enter your linkblue password.
Secure Login

This login is SSL protected