Identification of regenerative roadblocks via repeat deployment of limb regeneration in axolotls

Npj Regenerative Medicine
Donald M BryantJessica L Whited

Abstract

Axolotl salamanders are powerful models for understanding how regeneration of complex body parts can be achieved, whereas mammals are severely limited in this ability. Factors that promote normal axolotl regeneration can be examined in mammals to determine if they exhibit altered activity in this context. Furthermore, factors prohibiting axolotl regeneration can offer key insight into the mechanisms present in regeneration-incompetent species. We sought to determine if we could experimentally compromise the axolotl's ability to regenerate limbs and, if so, discover the molecular changes that might underlie their inability to regenerate. We found that repeated limb amputation severely compromised axolotls' ability to initiate limb regeneration. Using RNA-seq, we observed that a majority of differentially expressed transcripts were hyperactivated in limbs compromised by repeated amputation, suggesting that mis-regulation of these genes antagonizes regeneration. To confirm our findings, we additionally assayed the role of amphiregulin, an EGF-like ligand, which is aberrantly upregulated in compromised animals. During normal limb regeneration, amphiregulin is expressed by the early wound epidermis, and mis-expressing this factor le...Continue Reading

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Citations

Nov 14, 2019·Stem Cells·Valentina CigliolaPedro L Herrera
Jun 27, 2019·EvoDevo·Bess M MillerJessica L Whited
Oct 4, 2019·Development·Ben D CoxKenneth D Poss
May 10, 2019·Development·Hanna ReuterFlorenci Serras
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Jan 31, 2021·Cells·Valentina DaponteAntonella Forlino
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Jun 25, 2021·Frontiers in Cell and Developmental Biology·Maximina H Yun
Oct 5, 2021·Annals of the New York Academy of Sciences·Jennifer CableMerrit Romeike

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Methods Mentioned

BETA
amputation
amputations
RNA-seq
transgenic
biopsies
biopsy
in-vitro transcription

Software Mentioned

Graphpad Prism
Hmmer
Leica
Elements
ImageJ
Trinity
R
Leica Application Suite
RSEM
NIS

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