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.”
