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Role of the cardiac neural crest cells in heart development and regeneration

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Cells involved in tissue regeneration identified

A breakthrough discovery about tissue regeneration could shine new light on vertebrate evolution, and perhaps eventually lead to new therapeutic approaches.

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Neural crest cells are a group of cells that are formed during early embryonic development. They in turn give rise to a diverse cell lineage that includes cartilage and bone, muscle and neurons. “This cell population, neural crest, is only found in vertebrates,” explains Heart2019 project member Jan Stundl, currently based at the California Institute of Technology in the United States. “We are a successful species because of the neural crest – it is the reason we have teeth, for example. The neural crest is involved in almost every single part of our body.”

Investigating the cardiac neural crest

The Heart2019 project, which was coordinated by the University of South Bohemia in Czechia and supported by the Marie Skłodowska-Curie Actions programme, focused on a specific neural crest subpopulation – the cardiac neural crest. During early development, these cells migrate to the heart, and play a critical role in forming cardiac muscle. The project built on pioneering research that suggested that cardiac neural crest cells could be responsible for heart regeneration. “Using zebra fish – a model organism often used in developmental biology – the Bronner lab found that cardiac neural crest cells indeed contribute to regeneration,” says Stundl. “Neural crest cells are reactivated and help promote heart muscle formation.”

Cells responsible for heart regeneration

The question posed by the Heart2019 project was whether this regenerative phenomenon was unique to zebra fish, or common to other vertebrates. To answer this, three other vertebrate species were examined. These were the sturgeon – a fish similar to fish ancestors from millions of years ago – and the sea lamprey, a jawless fish which is primitive compared with jawed vertebrates. Finally, salamanders, which are amphibians that can regrow limbs and other body parts if they are cut off – were also examined. The project team focused on subadult populations of these species, collecting heart samples at different points of development. Data from these three unique vertebrates was then combined, to see if there is a common pattern of regeneration. “We discovered the neural crest is definitely involved in the regeneration process of sturgeon heart,” adds Stundl. “But what was really interesting was that we were able to actually identify the cell types derived from the neural crest that are important for heart regeneration.” Stundl explains that our peripheral nerves are usually coated with what are called Schwann cells. These cells come from the neural crest lineage. It is these cells that are reactivated and differentiate to promote tissue regeneration. The team found that these cells are responsible for regeneration of not only the heart, but other tissues as well.

Advancing our knowledge of evolution

A key finding of the project is that certain processes are shared across different types of vertebrate groups. This work will not only shine a light on how tissue regeneration works, but also advance our knowledge of evolution. Stundl notes that complex organisms such as humans lose the ability to regenerate, which is why studying less complex vertebrates is so essential for our understanding of regenerative ability. “One of the great things about fundamental research such as this is arriving at unexpected discoveries,” he says. “We are not so close at the moment to translating these findings into clinical applications, but further down the line, you never know.”

Keywords

Heart2019, cells, regeneration, therapeutic, neural crest, cardiac, heart

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