Japanese fire bellied newts have wowed scientists with their exceptional regenerative abilities that rival those of any other animal. A new study from the University of Tsukuba shows that these newts have developed a unique strategy for regenerating nearly every body part, from lost limbs to vital organs such as the heart and parts of the eye.
What's more is this newt retains its regenerative abilities even as an adult, whereas other amphibians with regenerative potential, such as axolotls, lose their ability once they have developed from a larva to a juvenile.
So what happens if a newt loses a leg, for example? A mass of cells, called a blastema, is generated at the stump, from which a new, fully functional leg is eventually regenerated. Researchers found that similar processes occur when the animal loses its tail, spinal cord, heart, brain, jaw and even parts of its eye, such as the retina or lens.
"The newt switches the cellular mechanism for limb regeneration from a stem/progenitor-based mechanism (larval mode) to a dedifferentiation-based one (adult mode) as it transits beyond metamorphosis," explained Chikafumi Chiba of the University of Tsukuba. "Delineating the mechanisms of these strategies will undoubtedly provide clues for regeneration in other species including mammals."
This discovery was made using transgenic Japanese fire bellied newts, which allowed researchers to track different types of muscle cells during limb regeneration in both larval and metamorphosed animals.
It was previously believed that either the skeletal muscle fiber cells (SMFCs) or muscle stem/progenitor cells (MPCs) contribute to new muscle in regenerated limbs of newts. For the latest study, a gene known to be active in SMFCs was inserted into single-celled newt embryos, which were then reared until the swimming larval stage, at three months of age, or the metamorphosed juvenile stage, at 16 months.
A red fluorescent protein linked to the gene was then monitored under a microscope during development and limb regeneration.
"We found that larval newts did not require muscle fiber cells to regenerate their amputated limbs," said Hibiki Tanaka, lead study author from the University of Tsukuba's Graduate School of Life and Environmental Sciences.
In other words, the study revealed that new muscle in larval newt regeneration tissue is primarily derived from muscle stem/progenitor cells, not skeletal muscle fiber cells.
However, after metamorphosis, the team found that the skeletal muscle fiber cells in the stump temporarily regress to a more primitive state, re-enter the cell cycle and proliferate to produce more muscle cells.
"Larval newts use stem/progenitor cells for new muscle in a regenerated limb while metamorphosed newts recruit muscle fiber cells in the stump for the same purpose," Tanaka added.
While no other animal can match the regeneration abilities of Japanese fire bellied newts, it is believed that the little amphibians will provide new insight into mammalian tissue regeneration, wound healing and repair.
Their findings were published in the March 30 issue of the journal Nature Communications.
