Limb muscle regeneration requires metamorphosis and body growth

Unknown to passers-by, a modest little creature with amazing abilities lives and reproduces in the forests and rice fields of Japan. Now Japanese researchers have discovered how the superpowers of these amphibians are unleashed.

In a study published this month in Scientific Reviews, researchers from the University of Tsukuba have revealed that during limb regeneration in newts, two developmental processes – metamorphosis and body growth – are necessary to provide the right conditions for the redeployment of muscle cells in the limb stump .

Newts, which are a semi-aquatic type of salamander, are like most other amphibians in that they undergo metamorphosis. But unlike their moms and dads, newts are capable of repeated limb regeneration – even in the adult stage after undergoing metamorphosis. In some species of newts, individuals who have already metamorphosed regenerate muscle mass by using dedifferentiation or reprogramming of muscle fibers in the limb stump, and mobilization of those fibers, to create muscle mass in the regenerating limb. .

“Unlike cell differentiation, where cells become more specialized, cell dedifferentiation is a process by which they become less specialized,” explains the lead author of the study, Professor Chikafumi Chiba. “Before our study, it was unknown whether metamorphosis or body growth was the key developmental process for muscle dedifferentiation.”

Researchers studied muscle cell dedifferentiation in the Japanese fire-bellied newt, Cynops pyrrhogaster, by tracking muscle fibers during limb regeneration while body growth and metamorphosis were experimentally delayed or advanced. The results suggest that metamorphosis and body growth are both necessary for muscle differentiation.

Conversely, when muscle tissues from larval newts were cultured with a physiologically active thyroid muscle fiber tracking has shown that these fibers can dedifferentiate independent of body growth and metamorphosis. These results indicate that newt muscle fibers have an inherent ability to dedifferentiate, but that body growth and metamorphosis are required for the fibers to activate this secret ability.

“ We suggest that developmental changes in the extracellular environment, or specialized niche, inhibit the activity of myogenic stem cells – cells that can differentiate into muscle fibers – and promote the latent ability of muscle fibers to dedifferentiate. In this way, the stem cells are compensated for by dedifferentiation, allowing newts to regenerate limb muscles throughout their life cycle,” says Professor Chiba.

The results of this study provide an important basis for future research on extracellular environments as well as the molecular mechanisms of dedifferentiation, such as the regulation of genes that underlie this phenomenon. This research will also contribute to a better understanding of regeneration, and perhaps even potential future medical treatments such as new therapies for disease and muscle damage.

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