Is salamander limb regeneration really perfect? First detailed anatomical and morphogenetic analysis of forelimb muscle regeneration in GFP‐transgenic axolotls as a basis for regenerative, developmental and evolutionary studies

Abstract

The axolotl Ambystoma mexicanum is one of the most used model organisms in evolutionary, developmental and regenerative studies, particularly because it is commonly said that it can reconstitute a completely normal and functional fore/hindlimb after amputation. Surprisingly, there is not a publication that tested the hypothesis that each regenerated forelimb muscle is really a ‘perfect’ copy of the original muscle. Here we describe the regeneration of the arm, forearm, hand, and some pectoral muscles in transgenic axolotls that express GFP in muscle fibers and report that: 1) there is a high percentage (43%) of muscle anomalies in the regenerated forelimbs; 2) however, on average in each regenerated forelimb there are anomalies in only 2.5% of the total number of muscles; 3) one of the most notable and common anomalies (in 35% of the regenerated forelimbs) is the presence of a fleshy coracoradialis at the level of the arm; this is a particularly remarkable configuration because in axolotls and in urodeles in general this muscle only has a thin tendon at the level of the arm; 4) during forelimb muscle regeneration there is a clear proximo‐distal and radio‐ulnar morphogenetic gradient but also a ventro‐dorsal gradient, which to our knowledge was not previously reported in the literature. We discuss the broader implications of these observations for regenerative, evolutionary, developmental and morphogenetic studies.Grant Funding Source: Start‐up package of Howard University College of Medicine