In the mouse fetus, the differentiation of intestinal lining into stomach lining happens rapidly, during a window of only one day, around the 12th and 13th days of gestation. (The corresponding period in the human fetus is during the 8th to 10th weeks.)
"We found that the epithelium [lining layer] is malleable, and depends completely on this pathway to instruct it to become stomach," says Shivdasani. "In the absence of this pathway, the epithelium would develop into the default intestinal state."
In experiments in mice, and with cultured mouse stomach and intestinal tissue, the scientists demonstrated that the signals that drive the differentiation of stomach lining are sent by a layer of cells, known as mesenchyme, that lie directly beneath the intestinal lining. The key player in the signaling pathway, they found, is a transcription factor a protein that governs the expression of genes under its control called Barx1. The main action of Barx1 in stomach lining formation is to block signaling through another pathway known as Wnt, the scientists found.
"Barx1 gives us a handle on what elements of the pathway might allow the stomach to differentiate abnormally into intestine as a result of injury to the stomach lining, setting the stage for cancer," Shivdasani says.
"These research findings offer the hope of identifying a protein marker that can be used to screen for these diseases and even to serve as a target for newly designed forms of therapy," said Robert Mayer, MD, director of Dana-Farber's Center for Gastrointestinal Oncology, who was not involved
'"/>
Contact: Bill Schaller or Richard Saltus
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
4-Apr-2005