Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae

Cell tracing and histological observations indicate that zebrafish tail muscle do not dedifferentiate during regeneration. Technical limitations did not allow us to trace tadpole limb cells, nevertheless we observed no signs of dedifferentiation histologically. However, ultrastructural and gene expression analysis of regenerating muscle in tadpole tail revealed an unexpected dedifferentiation phenotype. Further histological studies showed that dedifferentiating tail fibres did not enter the cell cycle and in vivo cell tracing revealed no evidences of muscle fibre fragmentation. In addition, our results indicate that this incomplete dedifferentiation was initiated by the retraction of muscle fibres.Our results show that complete skeletal muscle dedifferentiation is less common than expected in lower vertebrates. In addition, the discovery of incomplete dedifferentiation in muscle fibres of the tadpole tail stresses the importance of coupling histological studies with in vivo cell tracing experiments to better understand the regenerative mechanisms.While all vertebrates are able to repair certain injured tissues and organs, like muscle and liver, only lower vertebrates retain the ability to regrow complex appendages like fins, tails and limbs after amputation. An immense research effort has been made into uncovering the differences behind the disparity in regeneration ability between lower, regenerating vertebrates, and the non-regenerating, higher vertebrates. One of the main differences resides in the formation of the blastema, a structure composed of highly proliferative progenitors that will give rise to the new tissues. Mammals generally fail to form this structure [1-3]. In amphibians and fish, blastema formation happens right after wound healing and relies on the dedifferentiation of mature cells [4-6] and/or the activation of adult stem cells [7-10]. Dedifferentiation, or loss of differentiation characteristics followed by the acquisition of progenitor feature