AsianScientist (Apr. 6, 2016) – Research led by Associate Professor Chikafumi Chiba at the University of Tsukuba, has shed light on the newt’s exceptional regenerative ability and may provide further insight into regeneration in other species, including mammals. The work was published in Nature Communications.
When we are wounded, our bodies, and those of other mammals, generally respond by sealing the wound with scar tissue. The newt, however, is a master of regeneration—it has evolved unique strategies that allow it to repeatedly regenerate lost tissues.
When 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 eventually grows. No other animal can match its regenerative abilities in body parts, including the limbs, the tail and spinal cord, parts of the eye, the brain, the heart and the jaws.
What is more, they are unique in having this ability even as an adult. Other amphibians with regenerative potential, such as axolotls, lose this ability once they metamorphose from a larva to a juvenile.
The researchers made the exciting discovery that the mechanism for regeneration in the larval newt is different to the one used after metamorphosis. This discovery was made using transgenic newts, the use of which has only recently been made possible.
Using transgenic Japanese fire bellied newts, the team were able to track different types of muscle cells during limb regeneration in both larval and metamorphosed animals. It had been suggested previously that either skeletal muscle fiber cells (SMFCs) or muscle stem/progenitor cells (MPCs) contribute to new muscle in regenerated limbs of newts.
SMFCs make up skeletal muscles, which are one of the three major types of muscles, while MPCs are the dormant predecessors of muscle fiber cells and are located within muscle fibers. They can be triggered to proliferate for both self-renewal and specialization into muscle fiber cells.
The researchers inserted a gene known to be active in SMFCs into single-celled newt embryos. The gene was linked to a red fluorescent protein which could be switched on and off at precise times. Then, selected transgenic newts had a limb removed under anesthesia and the fluorescence of the tissues in them was monitored during development and limb regeneration.
“We found that larval newts did not require muscle fiber cells to regenerate their amputated limbs,” said Mr. Hibiki Tanaka, lead author of the study.
These experiments showed that the new muscle in larval newt regeneration tissue is primarily derived from muscle stem/progenitor cells, not skeletal muscle fiber cells. In contrast, after metamorphosis, the team found that the skeletal muscle fiber cells in the stump temporarily regress to a more primitive state, that is, they become dedifferentiated. The cells then 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.
Next, the researchers looked at whether or not the tissues in the limb strictly regenerated the same tissue types. After grafting various skin, bone, limb and muscle tissues from transgenic newts onto normal newts, the team discovered that the tissues faithfully regenerated themselves.
“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,” Chiba explained.
“Delineating the mechanisms of these strategies will undoubtedly provide clues for regeneration in other species, including mammals.”
Thus, while we may never have the incredible regenerative powers of the newt, it is likely that this little amphibian will continue to provide us with insights into mammalian tissue regeneration, wound healing and repair.
The article can be found at: Tanaka et al. (2016) A Developmentally Regulated Switch from Stem Cells to Dedifferentiation for Limb Muscle Regeneration in Newts.
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Source: University of Tsukuba; Photo: Kenta Hayashi/Flickr/CC.
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