Retinoic acid receptor regulation of epimorphic and homeostatic regeneration in the axolotl
Abstract
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 in skeletal integrity leading to long bone regression and loss of skeletal turnover. Overall, mechanisms were identified that regulate RAR's multifaceted roles in the salamander limb including regulation of skeletal patterning during epimorphic regeneration, skeletal tissue differentiation during regeneration, and homeostatic regeneration of intact limbs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2017
- Source ID
- 10.1242/dev.139873
Entities
People
- James R Monaghan
- Judith Piet
- M. Nguyen
- Malcolm Maden
- Pankhuri Singhal
- S. Randal Voss
- Sandra J. Shefelbine
Organizations
- National Science Foundation
- Northeastern University
- United States Army Research Laboratory
- University of Florida
- University of Kentucky