Researchers have identified how a key molecular pathway in salamanders is different than in mammals, possibly revealing the amphibians’ secret for regrowing their body parts. The findings tell us more about the mechanisms behind regeneration, and maybe one day they could be useful for regenerating human cells.

Salamanders are the only adult vertebrates who can regenerate full limbs. In fact, they’re able to regenerate an impressive repertoire of complex structures, including parts of their hearts, eyes, spinal cord, and tails, according to Max Yun from University College London. Regeneration depends on the ability of various adult cell types to undergo natural reprogramming. That means muscle cells, for example, must lose their muscle identity to help give rise to new cells that’ll form the replacement structure. 

Yun and colleagues decided to focus on extracellular signal-regulated kinase (ERK) activation in cells derived from the red-spotted newt (Notophthalmus viridescens, pictured). ERK is a pathway for proteins to communicate a signal from the surface of a cell to the nucleus where the genetic material can be found. 

They found that the ERK pathway must be constantly active for salamander cells to be reprogrammed. This sustained activation allows muscle cells to re-enter certain parts of the cell cycle. 

In contrast, the mammalian equivalent of the ERK pathway is not fully active in mouse cells. The scientists only observed transient ERK activation -- which explains why we and other mammals can’t regrow our entire limbs (although maybe a fingertip or a portion of the liver). The team then added a piece DNA that allows mammalian cells to produce a protein that activates the pathway. Forcing the pathway to be constantly active gives mammalian cells more potential for reprogramming and regeneration. 

“We’re thrilled to have found a critical molecular pathway, the ERK pathway, that determines whether an adult cell is able to be reprogrammed and help the regeneration processes,” Yun says in a news release. “Manipulating this mechanism could contribute to therapies directed at enhancing regenerative potential of human cells.”

Next, the researchers are trying to understand how the ERK pathway is regulated and what other molecules are involved in the process. 

The work was published in Stem Cell Reports this week. 

[University College London via The Conversation]

Images: Henk Wallays CC BY-NC 3.0 (top, bottom) & UCL (middle)