Reviewed by Alex SmithAug 18 2021
Researchers used blue light to gain a key insight regarding the main signaling pathway in tissue maintenance, cancer genesis and embryo development.
Illinois researchers developed a method that makes membrane-bound receptors reactive to light, triggering the Wnt pathway, important in embryonic development and cancer. Image Credit: Kai Zhang.
At the University of Illinois Urbana-Champaign, scientists have come up with a new approach that makes use of blue light to trigger the Wnt (pronounced as “wint”) signaling pathway in frog embryos.
According to the researchers, a wide range of roles is played by the pathway in animal and human development, and the potential to control it with light will enable scientists to gain better insights into its assorted functions.
Under the guidance of Kai Zhang, a professor of biochemistry, and Jing Yang, a professor of comparative biosciences, the researchers published the study in the Journal of Molecular Biology. The paper was selected as a featured communication, representing the top 1% of papers.
The activation of the Wnt pathway is done by a receptor on the surface of the cell that tends to induce a cascade response inside the cell. Zhang stated that it could be catastrophic when the signal is too little or too much. This makes it very hard to study the pathway with the help of standard methods 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.
Jing Yang, Professor of Comparative Biosciences, University of Illinois at Urbana-Champaign
Zhang feels that it is very hard to reach the balance required with standard methods to controlling such pathways, like chemical stimulation. For this issue to be addressed, scientists engineered the receptor protein to respond to blue light. With the help of Zhang’s method, it is possible to fine-tune the Wnt level by controlling the light’s duration and intensity.
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.
Kai Zhang, Professor of Biochemistry, University of Illinois at Urbana-Champaign
“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,” Zhang added.
The newly developed method was demonstrated by the researchers and its sensitivity and tunableness were confirmed by prompting spinal cord and head development in frog embryos.
Furthermore, the researchers hypothesize that their method can be applied to other membrane-bound receptors that have been hard to target, as well as other animals that share the Wnt pathway, enabling a better insight into the way these pathways control development, and what takes place when they are over- or 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.
Jing Yang, Professor of Comparative Biosciences, University of Illinois at Urbana-Champaign
Moreover, the scientists believe that their light-based method for studying Wnt could illuminate cancer research and tissue repair in human tissues.
Zhang stated, “Because cancers often involve overactivated signaling, we envision that a light-sensitive Wnt activator could be used to study cancer progression in live cells. 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.”
This study was financially supported by the National Institute of General Medical Sciences and the National Institute of Environmental Health Sciences within the National Institutes of Health.
Journal Reference:
Krishnamurthy, V. V., et al. (2021) Optogenetic Control of the Canonical Wnt Signaling Pathway During Xenopus laevis Embryonic Development. Journal of Molecular Biology. doi.org/10.1016/j.jmb.2021.167050.