Wnt is activated by receptors on the cell surface, which trigger a cascade of reactions within the cell. Too many or too few signals can be catastrophic, which makes it very difficult to study this pathway using standard techniques that stimulate 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: Although insufficient Wnt signaling can cause tissue repair failure, it may lead to elevated Wnt signaling in cancer.
It is difficult to achieve the necessary balance through standard methods to regulate these pathways, such as chemical stimulation. To solve this problem, the researchers designed the receptor protein to respond to blue light. In this way, they can fine-tune the Wnt level by adjusting the intensity and duration of the light.
"Light as a treatment strategy has been used in photodynamic therapy, which has the advantages of biocompatibility and no residual effect in the exposed area. However, most photodynamic therapies usually use light to produce high-energy chemicals, such as reactive oxygen species. Without distinguishing between normal tissues and diseased tissues, targeted therapy becomes impossible," Zhang said: "In our work, we have shown that blue light can activate signaling pathways in different compartments of frog embryos. We envision right The spatially defined stimulation of cell function can alleviate the challenge of off-target toxicity."
The researchers demonstrated their technology and verified its adjustability and sensitivity by promoting the development of the spinal cord and head of frog embryos. They hypothesized that their technology could also be applied to other membrane-bound receptors that have proven difficult to target, as well as other animals that share the Wnt pathway, to better understand how these pathways regulate development and what happens when they end.
"As we continue to expand our light-sensitive system to cover other basic signaling pathways for embryonic development, we will provide the developmental biology community with a set of valuable tools that can help them determine the signal results behind many developmental processes," Yang said.
Researchers also hope that the light-based technology they use to study Wnt can illuminate tissue repair and cancer research in human tissues.
"Because cancer usually involves over-activated signals, we envision that light-sensitive Wnt activators can be used to study cancer progression in living cells," Zhang said. "Combined with live cell imaging, we will be able to quantitatively determine what can transform normal cells into cancerous cells. The signal threshold provides the main data for the development of targeted specific treatments in precision medicine in the future."
