Casting Doubt on Latent Regenerative Mechanisms in Mammals

Demonstrations such as the unusual regenerative capacity of MRL mice have bolstered the idea that we mammals retain the vestiges of an ability to regenerate shared with lower animals such as salamanders - but suppressed or buried in some way. Hence work on deciphering the mechanisms of limb and organ regeneration in a variety of species could lead to the ability to turn on similar regeneration in humans. This work casts doubt on that view, however, suggesting that exceptional regeneration is not an ancient process shared across many species:

Tiny and delicate it may be, but the red spotted newt (Notophthalmus viridescens) has tissue-engineering skills that far surpass the most advanced biotechnology labs. The newt can regenerate lost tissue, including heart muscle, components of its central nervous system and even the lens of its eye. Doctors hope that this skill relies on a basic genetic program that is common - albeit often in latent form - to all animals, including mammals, so that they can harness it in regenerative medicine.

Attempts to analyse the genetics of newts in the same way as for humans, mice and flies have so far been hampered by the enormous size of the newt genome, which is ten times larger than our own. [Researchers] therefore looked at the RNA produced when genes are expressed - known as the transcriptome - and used three analytical techniques to compile their data. The team compiled the first catalogue of all the RNA transcripts expressed in N. viridescens, looking at both primary and regenerated tissue in the heart, limbs and eyes of both embryos and larvae.

The researchers found more than 120,000 RNA transcripts, of which they estimate 15,000 code for proteins. Of those, 826 were unique to the newt. What is more, several of those sequences were expressed at different levels in regenerated tissue than in primary tissue. [The] findings add to existing evidence that the ability evolved recently, [such as] evidence that regenerating tissue in salamanders express proteins that are not found in other vertebrates.

"I no longer believe that there is an ancestral program that is waiting to be reawakened. However, I absolutely do believe it's possible to coax mammal tissues into regenerating to a greater degree with the lessons we learn from newts."



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