Image: Transgenic worms, Hofstenia miamia. Credit; Lorenzo Ricci, University of Harvard
Several species can regenerate body parts when they are lost, but few are better at regeneration than three-banded panther worms. If the acoel worms lose their head, they can regrow another one. Cut the worms in half, and in 8 weeks you will have two fully formed worms. You could cut them into several pieces and new worms would regenerate from each of the pieces. They are true masters of regeneration.
Hofstenia miamia is a marine worm about the size of a grain of rice. Studying H. miamia could unlock the secrets to whole-body regeneration, which could lead to the discovery of new methods of treating injuries and diseases.
Harvard University researchers have now developed a method of introducing foreign genes into the genome of H. miamia that are preserved consistently across generations through a process called transgenesis. Transgenesis is used by researchers to study how cells and tissues work in the body of an animal. Genes can be introduced that are not normally present, and those genes will then be preserved across future generations. Researchers can also remove genes from the genome to determine the function of the genes.
The researchers, led by Manasi Srivastava, Ph.D., associate professor of organismic and evolutionary biology and curator of invertebrate zoology in the Museum of Comparative Zoology at Harvard University, used their new technique to make the worms glow in the dark. A gene was introduced into embryonic cells which coded for proteins that fluoresce under UV light. The transgenic worms took around 8 weeks to generate from the embryonic cells, with their epidermis, gut, and muscles glowing red or green under UV light.
The fluorescent markers allowed the researchers to study the worms in much greater detail and observe how cells look inside the animal and how they interact with each other. Through precision genetic manipulation, the researchers switched off certain genes and successfully disrupted the ability of the worms to regenerate. Further studies should uncover the specific genes that are required for full-body regeneration. The researchers have already identified several DNA switches that appear to be control genes for whole-body regeneration.
The researchers have gained insights into how muscle fibers in the worms connect with each other and with other cells and have shown they provide structure and support, akin to a skeleton in vertebrates. The muscle cells may do more than provide support and allow the worms to move. They could, for instance, play an important role in storing and communicating information on the body parts that need to be regenerated.
The researchers are now studying a population of pluripotent stem cells that are essential for regeneration. The cells, called neoblasts, can produce any other cell in the body, including skin cells, gut cells, muscle cells, and neurons.
“We don’t know how any one of these cells actually behave in the animal during regeneration,” said Srivastava. “Having the transgenic worms will allow us to watch the cells in the context of the animal as it regenerates.”
You can read more about the study in the paper – Transgenesis in the acoel worm Hofstenia miamia – which was recently published in the journal Developmental Cell. DOI: 10.1016/j.devcel.2021.10.012