Research led by Kai Zhang, a professor of biochemistry, and Jing Yang, a professor of comparative biosciences, at the University of Illinois Urbana-Champaign developed a way to activate the Wnt (pronounced “wint”) signaling pathway in frog embryos using blue light. This pathway plays a decisive and versatile role in animal and human development, the ability to manipulate it with light will allow researchers to better study its assorted functions, the team says. The team published its work in the Journal of Molecular Biology. This study illustrates for new understanding about signal pathways, tissue maintenance and cancer genesis, hopefully in human tissues, perhaps in the near future.

The Wnt (acronym for 'Wingless/Integrated' in genetics) pathways are a class of signal transduction pathways, which initiates due to a receptor on the cell surface that triggers a cascade response within the cell.

Too much or too little signal can be disastrous, Zhang said, making it very difficult to study the pathway using standard techniques for stimulating cell-surface receptors.

“During embryonic development, Wnt regulates the development of many organs such as the head, spinal cord and eyes. It also maintains stem cells in many tissues in adults: While insufficient Wnt signaling leads to the failure of tissue repair, elevated Wnt signaling may result in cancer,” Yang said.

A right set of equilibrium for signaling is hard to obtain with the standard approaches to regulating such pathways, such as chemical stimulation, Zhang said. To overcome this the experts engineered the receptor protein to respond to blue light, ensuring they can fine-tune the Wnt level by modulating the intensity and duration of the light.

“Light as a treatment strategy has been used in photodynamic therapy, with the advantages of biocompatibility and no residual effect in the exposed area. However, most photodynamic therapy typically uses light to generate high-energy chemicals – for example, reactive oxygen species – without differentiating between normal and diseased tissues, making it impossible to target treatment,” Zhang said. “In our work, we have demonstrated that blue light can activate a signaling pathway within different body compartments of frog embryos. We envision that a spatially defined stimulation of cell functions could mitigate the challenges of off-target toxicity.”

A demo by the scientists for the aforementioned technique and verified its tunableness and sensitivity by prompting spinal cord and head development in frog embryos. They further theorized that their technique could be applied to other membrane-bound receptors that have proved difficult to target, as well as other animals who share the Wnt pathway, allowing a greater understanding of how these pathways regulate development; what happens when they are over/under-stimulated.

“As we continue expanding our light-sensitive systems to cover other essential signaling pathways underlying embryonic development, we will provide the developmental biology community with a valuable set of tools that can help them determine the signaling outcomes underlying many developmental processes,” Yang said.

“Because cancers often involve overactivated signaling, we envision that a light-sensitive Wnt activator could be used to study cancer progression in live cells,” Zhang said. “In combination with live-cell imaging, we would be able to quantitatively determine the signaling threshold that could transform a normal cell into a cancerous one, therefore providing primary data for target-specific therapeutic development in future precision medicine.”