Tuesday, June 7, 2016

Is the ability to regenerate lost limbs lurking in our genes?

Study reveals hidden DNA that could be 'reawakened'

If a zebrafish loses a part of its fin, regeneration genes will kick in to regrow the tissue that was injured.

Researchers at Duke University have now uncovered the mechanism that activates these genes, to better understand what drives regeneration. These newfound 'enhancer elements' could be used to help mammals, including humans, regrow body parts, the researchers say.

The green signal in these images of an injured zebrafish heart and a fin indicate the activity of a gene that enhances tissue regeneration.

Many creatures have been observed as having the ability to regenerate tissue to repair damaged body parts, including zebrafish and salamanders. Mice and flies have also been found to contain regeneration genes, and even humans have been found to have 'counterparts,' to the genes that allow this type of tissue regrowth to happen.

In the new study, researchers sought to find out if DNA sequences exist to regulate the activity of these genes. These sequences would turn on regeneration genes in injured tissue and keep them on until regeneration is complete.

Zebrafish are able to repair damaged fins and even damaged heart tissue with genes called fibroblast growth factors and neuregulin 1, respectively.

The team discovered that in zebrafish, 'tissue regeneration enhancer elements' turn on the regeneration genes at the site of an injury. These could be engineered to allow other animals to regenerate, the researchers say.

'We want to know how regeneration happens, with the ultimate goal of helping humans realize their full regenerative potential,' said Kenneth D. Poss, PhD, senior author of the study and professor of cell biology at Duke University School of Medicine.

'Our study points to a way that we could potentially awaken the genes responsible for regeneration that we all carry within us.'

In zebrafish a gene called leptin b is turned on in injured fins or heart, discovered Junsu Kang, PhD, lead author of the study.

Scouring through thousands of base pairs around this gene, the researcher found distinct enhancer elements relating to each location.

By fusing the sequences to the two regeneration genes, the researcher created a zebrafish with superior fin and heart regeneration capabilities. The team then tested these elements on mice.

This revealed that the 'borrowed' enhancer elements from the zebrafish genome would turn on the regeneration genes in the injured paws and hearts of mice.

'We are just at the beginning of this work, but now we have an encouraging proof of concept that these elements possess all the sequences necessary to work with mammalian machinery after an injury,' said Poss.

As the capabilities progress, the researcher speculates that the elements could also be used in conjunction with genome-editing technologies to improve regeneration in mammals, including humans.

'We want to find more of these types of elements so we can understand what turns on and ultimately controls the program of regeneration,' said Poss.

This newly discovered element could one day help to repair and regrow damaged or missing body parts, the researcher says.

'There may be strong elements that boost expression of the gene much higher than others, or elements that activate genes in a specific cell type that is injured.

'Having that level of specificity may one day enable us to change a poorly regenerative tissue to a better one with near-surgical precision.'


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