Light can trigger key signaling pathway for embryonic development,
cancer

Date:
August 17, 2021
Source:
University of Illinois at Urbana-Champaign, News Bureau
Summary:
Blue light is illuminating new understanding of a key signaling
pathway in embryo development, tissue maintenance and cancer
genesis. Researchers have developed an approach using blue light
to activate the Wnt signaling pathway in frog embryos. The pathway
plays a wide variety of roles in animal and human development,
and the ability to regulate it with light will allow researchers
to better study its assorted functions, the team says.



FULL STORY ==========================================================================
Blue light is illuminating new understanding of a key signaling pathway
in embryo development, tissue maintenance and cancer genesis.


========================================================================== Researchers at the University of Illinois Urbana-Champaign developed
an approach using blue light to activate the Wnt (pronounced "wint")
signaling pathway in frog embryos. The pathway plays a wide variety of
roles in animal and human development, and the ability to regulate it
with light will allow researchers to better study its assorted functions,
the team says.

Led by Kai Zhang, a professor of biochemistry, and Jing Yang, a professor
of comparative biosciences, the research team published its work in
the Journal of Molecular Biology, where it was chosen as a featured communication, representing the top 1% of papers.

The Wnt pathway is activated by 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.

It is very difficult to achieve the necessary balance with standard
approaches to regulating such pathways, such as chemical stimulation,
Zhang said. To address this, the researchers engineered the receptor
protein to respond to blue light. With this approach, 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." The researchers demonstrated their technique and verified its tunableness and sensitivity by prompting spinal cord and head development in frog embryos. They hypothesize their technique also 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 --
and what happens 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," Yang said.

The researchers also hope their light-based technique for studying Wnt
can illuminate tissue repair and cancer research in human tissues.

"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." ========================================================================== Story Source: Materials provided by University_of_Illinois_at_Urbana-Champaign,_News_Bureau.

Original written by Liz Ahlberg Touchstone. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Vishnu V. Krishnamurthy, Hyojeong Hwang, Jia Fu, Jing Yang,
Kai Zhang.

Optogenetic Control of the Canonical Wnt Signaling Pathway During
Xenopus laevis Embryonic Development. Journal of Molecular Biology,
2021; 433 (18): 167050 DOI: 10.1016/j.jmb.2021.167050 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210817193016.htm

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