Embryonic stem cells stand poised to grow into various tissues, but are held in check by chemical switches that keep the necessary genes turned off. Researchers at the Salk Institute for Biological Studies found that genes responsible for limb regeneration – in this case the snipped tail of a zebrafish – are held in a similarly poised state by those same chemical switches.

It turns out that both embryonic stem cells and regenerative cells of the fish tail require enzymes called demethylases to release them from the poised state. In fact, zebrafish missing one of those enzymes are unable to re-grow their tail, something they routinely do in about a week.

A press release from the Salk Institute quotes first author Scott Stewart, postdoctoral scholar and CIRM training grant recipient, as saying:

“This is the first real molecular insight into what is happening during fin regeneration. Until now, how amputation is translated into gene activation has been like magic.”

While this sort of regeneration is common in fish and certain amphibians, it is unheard of in mammals. The Salk team plans to use this new finding to ask more specific questions about how we might be able to cross the barrier and induce limb regeneration in mammals.

The Salk Institute press release quotes the senior author Juan Carlos Izpisúa Belmonte, as saying:

“This finding will help us to ask more specific questions about mammalian limb regeneration: Are the same genes involved when we amputate a mammalian limb? If not, what would happen if we turned them on?”

 Proceedings of the National Academy of Science: November 24, 2009
CIRM funding: Scott Stewart (T3-00007-1)

D.G.