October 25, 2001
Cell signaling pathways: ‘Wnt’ family of genes governs important cell functions from zebrafish to humans
By Pamela Wyngate
HS News & Community Relations
A visitor to Dr. Randall Moon’s lab may encounter zebrafish and Xenopus laevis (frogs), as well as mouse and human cells. The common thread linking the fish, frog, mouse and human in the Moon lab is the Wnt-family of genes expressed in all of these organisms. Moon, professor of pharmacology and Howard Hughes Medical Institute investigator, studies the communication between cells in what are called the Wnt signaling pathways.
“Wnts are secreted proteins that signal between cells, telling neighboring cells to change their behavior, proliferation or what they will become,” explains Moon. “By studying Wnts in these diverse model systems we can tease apart how the Wnt pathways work and what are their normal functions.”
Wnt signaling pathways are similar to a cellular version of the children’s game Telephone, where children repeat a message to a neighbor sitting in a circle. In the game, the message may become garbled and nonsensical after a certain number of repetitions. In biology, where the children are represented by proteins, a confused message can cause genetic mutations resulting in cancer. In order to discern how and why a message gets altered, Moon investigates the Wnt signaling pathway from the ground up.
“Basically, the better you understand the normal biology of the pathway, the better you’re able to understand why it’s transforming-why it causes cancer,” says Moon. “The particular work that goes on in my lab spans from the very reductionist biochemical approach of identifying new proteins in the Wnt pathways and how they work, all the way to the organismic level of what the pathways are doing in vertebrates.”
What researchers have found over the years through genetics, biochemistry and cell biology is that there are very specific and sophisticated protein-protein interactions that lead to the Wnt signal changing gene expression, according to Moon.
One example of the normal functions of Wnt signaling is that it specifies the dorsal (back) side of vertebrate embryos. Moon and colleagues have found that soon after fertilization of frog eggs, the Wnt pathway becomes activated in a particular side of the embryo-leading to gene expression that in turn “tells” that side of the embryo to become the dorsal side. Another example of the functions of Wnt signaling is in the developing nervous system where Wnts help tell potential neural cells what to become.
Specific human cancers linked to inappropriate activation of the Wnt pathway include colorectal cancer and certain melanomas, the most aggressive form of skin cancer. The basic science gleaned from research in Moon’s lab may lead to drugs designed to target specific parts of the Wnt pathway, allowing intervention in various cancers.
“Signaling pathways are never working just by themselves, so one of the big questions for the future is how do you place the function of a Wnt signaling pathway in a greater context,” says Moon. “How does this signaling pathway interact with all of the other signaling pathways in development and disease?”
Moon presents “WNT Signaling Pathways in Development and Disease” at noon on Thursday, Nov. 1 in Turner Auditorium-room D-209 of the Health Sciences Center. The lecture is part of the Science in Medicine series and is open to everyone.
Moon received his Ph.D. in zoology at the UW in 1982. He was a postdoctoral fellow in the Division of Biology at the California Institute of Technology (1982 to 1985). In 1985 Moon joined the UW faculty as an assistant professor of pharmacology, becoming a professor in 1997. He received a Research Career Development Award from the National Institutes of Health for 1990 to 1994. In 1994 he was named an associate investigator with the Howard Hughes Medical Institute, becoming an investigator in 1997. Moon is a fellow of the American Association for the Advancement of Science.
