UC Irvine Researchers Discover Molecular Interaction That Gives New Insight On How Cells Communicate

Irvine, Calif., Feb. 16, 2000 — UC Irvine researchers have discovered a new molecular interaction involved in embryo development that is providing fundamental information on how cells communicate during the important early stages of development.

Working with scientists at the National Institute for Basic Biology in Okazaki, Japan, the researchers identified a novel interaction among molecules that regulate the development of the head, back and central nervous system. Their discovery shows for the first time the linking of molecules from two key growth-regulating genes and potentially may lead to a better understanding of cellular abnormalities that can lead to colon and skin cancers.

Their findings appear in the Feb. 17 issue of Nature.

"This gives us new insight on how molecules act during the crucial early stages of development," said Ken W.Y. Cho, professor of developmental and cell biology at UCI who, along with Hiroshi Shibuya of the National Institute of Basic Biology, is a lead researcher in this study.

Researchers observed the signaling pathways of two genes-named Wnt and TGF-ß-during the formation of frog embryos. During development, these pathways give the specific information that determines the role each cell will play. These signals travel through a series of intermediate molecules, called relay molecules, to the nucleus of a cell, where gene regulation occurs.

The UCI researchers have found that two relay molecules from the Wnt signaling pathway-named Lef and b-catenin-and one molecule from a member of the TGF-b signaling pathway-named Smad4-interact both physically and functionally. This means that the initial signals from the two gene pathways travel through these intermediate molecules for delivery to the cell nucleus.

"While it is already known that these two signaling pathways cooperate to regulate cellular events, this is the first time that their relay molecules have been shown to physically interact together instead of acting separately," Cho said.

Cho's main research interest lies in understanding the molecular activity that governs the formation of Spemann's Organizer, a region of the embryo that determines that the head, backbone, nervous system and muscles will develop in the right places. The interaction among the Lef, b-catenin and Smad4 molecules affects the formation of Spemann's Organizer. In addition, these molecules also determine other cell activity in both developing and adult organisms.

Aberrations in the normal function of these molecules have been linked to some types of cancers, such as skin and colon cancers, although the exact mechanism that leads to cancer is still not well understood. This new information adds to the researchers' understanding of how these molecules function normally, which improves the potential for someday better understanding how cancers arise. In addition to Cho and Shibuya, authors of the study are Minako K. Hashimoto, Souichi Ogata and Micheline N. Laurent of UCI's Department of Developmental and Cell Biology and Michiru Nishita and Naoto Ueno of the Department of Developmental Biology at the National Institute for Basic Biology. The study was funded by the National Institutes of Health and the Pew Scholars Program.