The Stowers Institute’s Pourquié Lab has demonstrated the importance of Beta-catenin, a key component of the Wnt-signaling pathway in the process of somite formation. The work has been published on the Web site of Nature Cell Biology and will appear in a future print issued. It was conducted using a novel real-time imaging technology.
The team analyzed the somite segmentation process that results in the formation of the vertebral column. This process is thought to be controlled by two components: a molecular oscillator (the segmentation clock), and the graded activity of several major signaling pathways (the gradient) in the presomitic mesoderm (PSM). The PSM is the middle layer of the three cell layers that form an early embryo. Wnt-signaling has been implicated in both these mechanisms, but precisely how was unclear until now.
In this work, the Pourquié team tested the importance of Beta-catenin, a protein that functions as the principal mediator of the Wnt-signaling pathway, in the process of somite formation. They showed that a newly identified Beta-catenin protein gradient in the PSM is critical in regulating mesoderm maturation. Real-time imaging experiments also demonstrated that, conversely, the segmentation clock is not caused by graded levels of Beta-catenin protein.
“We were able to demonstrate that increasing Beta-catenin protein levels dramatically alters PSM maturation,” said Alexander Aulehla, M.D., Senior Research Associate and first author on the paper. “But, by using the real-time imaging technique in mouse embryos, we could show that increasing Beta-catenin also corresponded with ongoing, even ectopic, oscillations of the segmentation clock, which controls the rate of somite development.”
“This work offers novel insights into how the mechanisms of maturation and oscillation in the PSM are controlled and how they are interconnected,” said Olivier Pourquié, Ph.D., Investigator and senior author on the paper. “Additionally, this project has allowed us to achieve the longstanding goal of visualizing the segmentation clock in real-time using fluorescence-based imaging, which is sure to impact other important projects in our lab”
Since joining the Stowers Institute in 2002, the Pourquié Lab has made a number of significant discoveries related to somite development. Somites eventually give rise to the vertebral column, which is malformed in people born with congenital scoliosis. It is believed that some cases of congenital scoliosis are caused by mutations related to the segmentation clock.
Additional contributing authors from the Stowers Institute include Winfried Wiegraebe, Ph.D., Director - Advanced Instrumentation and Physics; and Matthias Wahl, Ph.D., Postdoctoral Research Associate. Additional authors include Valerie Baubet, Ph.D., The Wistar Institute; Chuxia Deng, Ph.D., National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Makoto Taketo, M.D., Ph.D., Kyoto University; and Mark Lewandoski, Ph.D., NCI-Frederick, National Institutes of Health.
Dr. Pourquié also is an investigator with the Howard Hughes Medical Institute and a Professor in the Department of Anatomy & Cell Biology, The University of Kansas School of Medicine. Learn more about his work at www.stowers-institute.org/labs/PourquieLab.asp.
About the Stowers Institute
Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing and curing disease. The Institute was founded by Jim and Virginia Stowers, two cancer survivors who have created combined endowments of $2 billion in support of basic research of the highest quality.
Journal
Nature Cell Biology