Optogenetics Shapes Tissue to Reconstruct Epithelial Folding

Using optogenetics, researchers have guided the folding and shaping (morphogenesis) of tissues and cells that otherwise would not undergo this process.

Three examples of the tissue shapes created by the team at the European Molecular Biology Laboratory. The black-and-white square, circle, and triangle on the left correspond to the cells that were illuminated. On the right, three fruit fly embryos are shown in cyan, magenta, and yellow, demonstrating how the illuminated cells folded inwards after the light activation. Courtesy of Stefano De Renzis, EMBL.

Researchers at the European Molecular Biology Laboratory (EMBL) used precise light-mediated control of protein activity in biological tissues to reconstruct epithelial folding in embryonic Drosophila tissues. Epithelial folding is a developmental process where cells move inward and fold into the embryo, eventually giving rise to internal tissues like muscles.

“The great thing about using optogenetics to guide morphogenesis is that it is a very precise technique," said researcher Emiliano Izquierdo. "We were able to define various shapes, and by alternating the timing and strength of illumination, we could control how far the cells folded inwards.”

For its experiment, the team used cells that do not normally undergo the process of epithelial folding.

“We’ve uncoupled the link between the shape and function of the cell," said research leader Stefano De Renzis. "This allows us to, for the first time, build tissues in certain shapes without affecting the cell’s expertise.”

Example of optogenetics-guided tissue folding. Embryo 10 min after illumination (top panel), and one 13 min after (bottom panel). Light-activated cells have folded inward and thus moved downward, creating a furrow. Courtesy of Stefano De Renzis, EMBL.

The experiment was done in developing fruit flies, but since epithelial folding is a conserved process across evolution, De Renzis believes that the methods used in the EMBL experiment could be applicable in other organisms and ex vivo stem cell culture systems.

Results of the research show that it is possible to apply concepts of synthetic biology (e.g., precise orthogonal control over signaling pathways, guided cell behavior) to the field of tissue morphogenesis.

Normally, tissue differentiation and tissue shape are closely linked, but the researchers showed that it is possible to use optogenetics to direct tissue shape without interfering with gene regulatory networks and tissue-differentiation programs. This could have implications for tissue engineering, where it could be useful to shape any given tissue of interest without changing its fate.

The research was published in Nature Communications (doi:10.1038/s41467-018-04754-z).

Optogenetics: principles and approaches. Courtesy of EMBL.