Myocyte Dedifferentiation Drives Extraocular Muscle Regeneration in Adult Zebrafish

Abstract

EOM regeneration in adult zebrafish occurs by dedifferentiation of residual myocytes involving a muscle-to-mesenchyme transition. A mechanistic understanding of myocyte reprogramming may facilitate novel approaches to the development of molecular tools for targeted therapeutic regeneration in skeletal muscle disorders and beyond.

Regulation and phylogeny of skeletal muscle regeneration

“…Similarly, it has been shown in the adult electric fish (S. macrurus) that muscle repair following tail amputation also involves Pax7-positive SLCs, but not myofibre dedifferentiation (Weber et al, 2012). Interestingly, according to the muscle type, the zebrafish is capable of exploiting both strategies: extraocular muscle injury using partial myectomy of the lateral rectus showed no SLC contribution to muscle regeneration, instead, residual myocytes undergo dedifferentiation (Saera-Vila et al, 2015).…”

“…It would be interesting to explore the status of tumour suppressors using two structures that differ by their repair mechanism: such as the zebrafish extraocular muscle (dedifferentiation, (Saera-Vila et al, 2015)) versus the tail (SLCs).…”

“…Similarly, it has been shown in the adult electric fish (S. macrurus) that muscle repair following tail amputation also involves Pax7-positive SLCs, but not myofibre dedifferentiation (Weber et al, 2012). Interestingly, according to the muscle type, the zebrafish is capable of exploiting both strategies: extraocular muscle injury using partial myectomy of the lateral rectus showed no SLC contribution to muscle regeneration, instead, residual myocytes undergo dedifferentiation (Saera-Vila et al, 2015).Recently, other chordate models emerged to study the evolution of regenerative biology at the invertebrate-vertebrate transition. The basal chordate amphioxus shows a high regenerative potential and it is capable of regrowing both anterior and posterior structures during adult life, including neural tube, notochord, fin, and muscle after amputation (Somorjai et al, 2012).…”

“…These cells amplify upon amputation migrate toward the periphery of degrading myofibres and fuse. These and other studies suggest that amphioxus is a tractable model for regenerative myogenesis, and it has extensive regenerative capacities beyond those of more complex vertebrates (Somorjai et al, 2012).As another example, the crustacean Parhyale hawaiensis develops a blastema structure after It would be interesting to explore the status of tumour suppressors using two structures that differ by their repair mechanism: such as the zebrafish extraocular muscle (dedifferentiation, (Saera-Vila et al, 2015)) versus the tail (SLCs). …”

Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish

“…Indeed, adult zebrafish are able to regenerate both skeletal [4] and cardiac muscle [5, 6], as well as retina [7], spinal cord [8], liver [9] and fin [10, 11]. Our lab recently characterized a robust regenerative pathway in adult zebrafish extraocular muscles (EOMs) –a form of skeletal muscle– which is driven by myocyte dedifferentiation with no significant contribution of satellite cell [4]. Thus, we can now utilize a novel model for studying the mechanistic underpinnings of myocyte reprogramming via dedifferentiation.…”