New regulatory mechanism discovered for cell identify and behavior in form...( CINCINNATI Two proteins interact in...)

CINCINNATI Two proteins interact in a previously unknown molecular mechanism that may have broad implications in future studies looking for the causes of defective organs in fetuses, metastatic cancers and other diseases, according to researchers at Cincinnati Children's Hospital Medical Center.

Reporting their work in the Oct. 15 Genes & Development, the researchers said the mechanism coordinates cell identity and behavior in the forming organs of embryos.

"Our study helps address the current challenge of finding out where cell specificity comes from, how cells do what they do in the context of disease and development, and how these activities are regulated," said Aaron Zorn, Ph.D., a researcher in the division of Developmental Biology at Cincinnati Children's and the study's corresponding author. "This helps inform research into how we tell early stem cells what to become. If someone has diabetes, for example, how do we tell a cell to become a pancreas cell so it will produce insulin?"

The study involved embryos of Xenopus frogs, a species indigenous to Africa often used in early biomedical studies. The scientists discovered a signaling protein very common in developmental biology, Wnt11 (Wingless), has to be inhibited by the modulating protein Sfrp5 (Secreted Frizzled Related Protein), a known antagonist of Wnt. Without this restriction, Wnt signaling runs amok and the frog's foregut, liver and pancreas form improperly from a cascade of disorganized cell growth.

"We point out that Wnt has two key roles here one controlling the cell expression pathway to tell cells what they are supposed to be, and the other controlling the pathway for cell movement, behavior and adhesion," said Dr. Zorn, also associate professor of pediatrics at the University of Cincinnati (UC) College of Medicine. "Without Sfrp5 controlling what Wnt does in both pathways, things go horribly wrong in the developing foregut and its organs."