OREGON STATE UNIVERSITY

Genetic basis discovered for abdominal wall formation

05/03/2010

CORVALLIS, Ore. – Researchers at Oregon State University have identified the genetic mechanisms that control formation of the abdominal wall in mammals – a critical process that begins in the first trimester of pregnancy in humans, and if not done properly can lead to hernias or the need for corrective surgery.

By learning the genetic basis for this process, researchers say, it may ultimately be possible to create, from stems cells, the type of cells needed in this tissue formation, and use regenerative medicine to provide a permanent, effective and non-surgical treatment for this health problem.

The findings – recently published as the “paper of the week” in the Journal of Biological Chemistry – provide some of the basic information needed for future progress toward that goal, scientists say.

“We’re learning more about the regulatory networks that control the formation of organisms, including humans,” said Chrissa Kioussi, an associate professor in the OSU College of Pharmacy. “Much of this occurs during what’s called gastrulation, or the very early periods of gestation where genes direct cells to become different things, such as parts of the nervous system, soft tissues or muscles.”

Humans have about 20,000 genes, Kioussi said, but only about 1 percent of them are “homeobox” genes that become involved in specifying the fate of a cell. If all cells know what to become and where to go at a certain time, an animal such as a human ends up with all the parts it’s supposed to have – one head, two arms, two legs, a heart and all the other segments that work together.

However, those processes sometimes become misdirected, and one of the common mistakes is an incorrect formation of the abdominal wall, which can set the stage for hernias or other problems – often treatable only by surgery.

“Some of the genes involved in these processes are very primitive and have been doing the same thing for millions of years, and are found in animals ranging from fruit flies to humans,” Kioussi said. “But the cellular expression processes are still very complex, and we’re just now beginning to understand what controls them.”

In this case, she said, it was found that the transcription factors known as “Pitx2” and “T-box” play key roles in the formation of the abdominal wall. In laboratory mice in which the Pitx2 gene had been deleted, the abdominal wall completely failed to form and failed to enclose the internal organs.

As these molecular processes are identified, Kioussi said, it will give researchers a target to work with in pursuing tissue regeneration. Work of that type is already being done in creating cells to address such problems as diabetes and Parkinson’s disease, she said, and broader use of tissue regeneration could be possible in the near future. OSU scientists are planning to begin work in that field soon, Kioussi said.

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a part of the National Institutes of Health.