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New regulatory mechanism discovered for cell identify and behavior in forming organs
Date:10/31/2008

The Wnt signaling pathway is a complex network of proteins best known for their role in stimlating cell behavior during embryo development and in cancer. They also are involved in normal physiological processes in adult animals. Parts of the Wnt pathway have been conserved between species during the long course of evolution, all the way from simple roundworms to humans.

Previous research in Xenopus has established that a low level of activity from a molecule called B-catenin which promotes cell-to-cell adhesion and is part of the Wnt pathway is necessary to maintain accurate foregut formation and initiate liver and pancreas development. Unknown before the study by Dr. Zorn's team was which Wnt genes are involved and how Wnt and B-catenin activity are regulated along the frog's developing anterior-posterior body axis.

During the very early phases of embryo development when the organism is still essentially flattened layers of cells called an endoderm Dr. Zorn's team found Wnt's stimulation of B-catenin must be restricted in the anterior region so the tissue of forming foregut organs maintain its integrity. Their experiments showed that Sfrp5 steps in at the right time and place to repress Wnt signaling, allowing the cells to form an epithelial sheet, or lining an essential step in organ development.

In one experiment, when researchers removed the Sfrp5 protein, the resulting Sfrp5-depleted Xenopus embryos had smaller foregut cavities filled with unorganized early-stage endoderm cells, which were incapable of properly forming liver and pancreatic organs.

Dr. Zorn and colleagues said their results have possible implications in metastatic cancer. For one, Sfrp proteins are already known to be tumor suppressors that are genetically inactivated in some cancers as they progress to aggressive carcinomas. Carcinomas typically originate in epithelial cells which form linings surrounding the surfaces and cavities of many body st
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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