Rebuilding limbs, one cell at a time

Abstract

Key Findings New techniques for visualizing and interrogating single cells hold the key to unlocking the underlying mechanisms of salamander limb regeneration.

Wnt Signaling Coordinates the Expression of Limb Patterning Genes During Axolotl Forelimb Development and Regeneration

“…Transcriptomic studies have shown that developmental genes are re-expressed during limb regeneration ( Monaghan et al, 2009 ; Campbell et al, 2011 ; Monaghan et al, 2012 ; Knapp et al, 2013 ; Stewart et al, 2013 ; Voss et al, 2015 ; Bryant et al, 2017 ) and connective tissue cells in the regenerating limb become transcriptionally similar to limb bud cells ( Gerber et al, 2018 ). However, the similarities and differences between limb development and limb regeneration have yet to be satisfactorily explained [( Tanaka 2016 ; Leigh and Currie 2022 ) for review].…”

Multi-species atlas resolves an axolotl limb development and regeneration paradox

“…Limb regeneration has long been thought to mimic some aspects of limb development 3, 17, 44, 45 , offering a roadmap to establish strategies to regrow lost mammalian limbs. Our results here suggests that more complex and species-specific processes exist for both limb development and regeneration, even among regeneration-competent animals.…”

“…The AER supplies critical signaling ligands and its spatial organization contribute to the morphogen gradients to form a correctly patterned limb 2 . Interestingly, the leading limb regeneration model organism, the axolotl 3 , was suggested not to have an AER, as they lack a morphological ridge structure and some of the molecular AER markers [4][5][6][7] . Despite these findings, as .…”

“…The AER supplies critical signaling ligands and its spatial organization contribute to the morphogen gradients to form a correctly patterned limb 2 . Interestingly, the leading limb regeneration model organism, the axolotl 3 , was suggested not to have an AER, as they lack a morphological ridge structure and some of the molecular AER markers [4][5][6][7] . Despite these findings, as regeneration is thought to largely recapitulate development, salamander regeneration is considered to re-form AER-like cells to act as a signaling center apical-epithelial-cap, AEC, at the amputation plane [8][9][10] .…”

Limb development, evolution, and regeneration and repair: Part two

“…He proposes that the complexity of the nervous system and the adaptive immune system might have been a barrier to organ regeneration. Leigh and Curie 11 review the impact that advances in single‐cell transcriptomics, deep tissue imaging and genome engineering technologies had on the field of limb regeneration in salamanders. In particular, they highlight how these methods have clarified the lineage relationships of blastemal cells, and how they will likely help understanding the regenerative niche effect that characterizes the blastema.…”