The Genetics Behind Regeneration

Many animals are capable of regenerating complex body parts and restoring them to full functioning. Salamanders and planarians regrow damaged or missing body parts, while flatworms can replicate their entire bodies from minuscule components of themselves. The human body is comparatively limited in its ability to regenerate, as humans are only capable of renewing damaged organs such as the liver and skin. However, recent research in animal regeneration has revealed various stem cell strategies for regenerating body parts, that could one day be applied to humans.

As regenerative research in other species advances, understanding of the limits and possibilities of regeneration grows. A recent study conducted at Harvard University examined the regenerative process of three-banded panther worms to further evaluate the possibility in humans. Led by Assistant Professor Mani Srivastava, a team of researchers uncovered genes that control the process of whole-body regeneration, shedding new light on how animals are capable of accomplishing this.

The Harvard study may have unlocked the key to regeneration. In examining the process in worms, Srivastava and her team found that a section of noncoding DNA, previously believed to have no significant function, controls the early growth response gene, or EGR. “What we found is that this one master gene comes on [and activates] genes that are turning on during regeneration,” said postdoctoral fellow, Andrew Gehrke, who works in Srivastava’s lab. Upon activation, this “master control gene” commands a number of other processes.

Another significant finding of the study revealed that the genome in three-banded worms is dynamic and changes during the regenerative process. DNA in the worms’ cells, which is normally tightly folded and compact, had to change to make room for new areas of activation by physical opening up to create space. Gehrke was able to identify up to 18,000 regions that underwent change once the EGR was activated, revealing the critical nature of the gene in regeneration.

Not only does this study reveal new information about the regenerative process in worms, but it also helps to explain why humans are incapable of doing the same. Srivastava and her team suggest that there is a crucial difference between the wiring in humans and species capable of whole-body regeneration. Even though it also produces cells when in need of repair, the EGR in humans may be communicating with entirely different regions and thus, not triggering large scale regeneration.

In order to apply these findings to the human body, further research is necessary to ascertain the connections of EGR genes in other animals, including vertebrates with similar limited regeneration capabilities. “We’ve looked at some of these switches, but there’s a whole other aspect of how the genome is interacting on a larger scale, not just how pieces open and close,” said Gehrke.

Regeneration remains a developing field of study as this study scratches the surface of an incredibly complex biological process. Additional studies will need to be conducted to discover a method of adjusting master gene circuitry to reap the benefits of regenerative medicine.

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