Epigenetic Signaling Induces Species-Specific Head and Brain Growth in Flatworms

Biologists induced one species of flatworm—G. dorotocephal, top left—to grow heads and brains characteristic of other species of flatworm, top row, without altering genomic sequence. Examples of the outcomes can be seen in the bottom row of the image. [Center for Regenerative and Developmental Biology, School of Arts and Sciences, Tufts University.]

As if it were ripped straight from the pages of a classic sci-fi story or horror genre film, scientists from Tufts University have succeeded in inducing one species of flatworm to grow heads and brains characteristic of another species of flatworm, without altering genomic sequence. The impact of this work is that it may have uncovered physiological circuits acting as a new kind of epigenetic signaling pathway that could determine the fate of large-scale anatomical phenotypes.

The researchers found that head shape was not hard-wired by the flatworm’s genome and was able to be circumvented through the manipulation of chemo-electrical signaling pathways—suggesting, in part, that differences in species could be determined by the activity of bioelectrical networks. The Tuft’s investigators believe that their discovery may provide a better understanding of birth defects and regeneration by revealing a new pathway for controlling complex pattern formation.

“It is commonly thought that the sequence and structure of chromatin—material that makes up chromosomes—determine the shape of an organism, but these results show that the function of physiological networks can override the species-specific default anatomy,” explained senior author Michael Levin, Ph.D., professor at the Tufts Center for Regenerative and Developmental. “By modulating the connectivity of cells via electrical synapses, we were able to derive head morphology and brain patterning belonging to a completely different species from an animal with a normal genome.”

Understanding how body shape is determined and how to manipulate it is an important aspect of developmental and regenerative biology, as scientists could use that knowledge to rectify birth defects or possibly grow new tissues after injury. “These findings raise significant questions about how genes and bioelectric networks interact to build complex body structures,” Dr. Levin added.

The findings from this study were published recently in the International Journal of Molecular Science through an article entitled “Gap Junctional Blockade Stochastically Induces Different Species-Specific Head Anatomies in Genetically Wild-Type Girardia dorotocephala Flatworms.”

The researchers chose to study the free-living planarian flatworm G. dorotocephala since it has a remarkable regenerative capacity. By interrupting gap junctions—channels that connect cells together and provide a means of transcellular communication—Dr. Levin’s team was able to induce the development of different specific-specific head shapes. Moreover, the shape of the brain and the distribution of the worm's adult stem cells were also affected by these disruptions.

Interestingly, the ease with which a particular shape could be generated from a G. dorotocephala worm was proportional to the proximity of the target worm on the evolutionary timeline, i.e., the closer the two species were related, the easier it was to effect the change.

The scientists did notice, however that the anatomical changes were only temporary. Weeks after the planaria completed regeneration to the other species' head shapes, the worms once again began remodeling and re-acquired their original head morphology. Dr. Levin and his team are currently investigating how the reversion back to the original phenotype is occurring.

“We've demonstrated that the electrical connections between cells provide important information for species-specific patterning of the head during regeneration in planarian flatworms,” noted lead author Maya Emmons-Bell, an undergraduate researcher in Dr. Levin’s laboratory. “This kind of information will be crucial for advances in regenerative medicine, as well as a better understanding of evolutionary biology.”