Vanderbilt University Medical Center scientists deciphered how the Type III TGF-beta receptor leads to the formation of valves and dividing walls in the heart, reports the March 26th issue of Science.
Their findings have particular relevance to the families of children with congenital heart defects, the leading cause of birth defect-related deaths. About 1 in 100 children born each year in the United States have heart defects, yet little is known about the causes, and surgery is often the only treatment option.
Joey V. Barnett, Ph.D., assistant professor of Medicine and Pharmacology and a member of the division of Cardiovascular Medicine, is interested in the role of growth factors in heart development, particularly how the valves and septa-dividing walls-of the heart are formed.
Their formation begins when the heart is only a simple tube and cells in a region called the atrioventricular (AV) cushion receive a signal that tells them to change shape, pull away from their neighbors and migrate. Those cells eventually multiply and give rise to the heart's valves and septa.
It has been a mystery why only a small population of cells receives the signal to change.
"Their neighbors never undergo this epithelial-mesenchymal transformation," Barnett said. "We wanted to know why, so we asked what cell surface receptors are found on the cells that transform but are missing on the cells that do not."
Transforming growth factor-beta (TGF-beta) has been suspected to play a role in transformation of the AV cushion cells, so Barnett and Christopher B. Brown, Ph.D. focused on the different types of TGF-beta receptors.
In the current report, they show that the Type III TGF-beta receptor is found on those cells in the developing heart that undergo the transformation.
"If we use experimental techniques in an in vitro assay to block this receptor
on those cells, they don't transform," Barnett said. "Conversely, if we
introduce this receptor into c
Contact: Matt Scanlan
Vanderbilt University Medical Center