By Gila Z. Reckess
June 15, 2001
A recently discovered protein appears essential for lung development.
Mice unable to make a protein called fibroblast growth factor 9 (Fgf9) die at birth with under- developed lungs, researchers have found. They suggest that Fgf9 controls lung size and shape.
"We believe Fgf9 tells the lungs how big to grow," David M. Ornitz, M.D., Ph.D., said. "And we suspect it might be involved in some lung diseases ranging from cancer to fibrosis. Blocking Fgf9 may in the future be used to treat those conditions."
Ornitz, professor of molecular biology and pharmacology at the School of Medicine, led the study. The first author was Jennifer S. Colvin, Ph.D., a student in the school's M.D./Ph.D. program. The results were published in the June issue of the journal Development.
Fibroblast growth factors regulate cell growth and migration and therefore are integral to organ development. Because Fgf9 was discovered only recently, its role in development is unclear.
The medical school team developed a strain of mice lacking the gene for Fgf9 to determine how the protein's absence affects organ development. Of 138 offspring, nine died at birth with severely underdeveloped lungs. All nine lacked Fgf9. The surviving mice had at least one copy of the normal gene for Fgf9.
Eight embryos lacking Fgf9 were removed from their mothers before birth. At first, seven were breathing and had healthy, pink skin. But within 30 minutes, all seven had difficulty breathing and their skin turned blue. The researchers concluded that mice lacking Fgf9 survive embryonic development but die after birth, when they must get oxygen through their lungs instead of through the placenta.
Because these mice appeared to die from pulmonary complications, the researchers investigated the role of Fgf9 in the lungs. They found two main differences between the mice lacking Fgf9 and the healthy animals.
Lungs have a complex series of airways that range from large tubes to small branches. The airways in the mice lacking Fgf9 appeared normal during early embryonic development, when the larger tubes form. But later in development, the tubes failed to branch. Ornitz and his colleagues found Fgf9 localized to the surface lining of the lung. They therefore propose that it controls the extent of tissue surrounding the airways and subsequent branch development.
Second, the animals' lungs did not grow large enough to fill the chest cavity. They also were not as sharply contoured as normal lungs. The researchers therefore suggest that Fgf9 controls both lung size and shape.
If so, Fgf9 eventually might be useful for regenerating adult lung tissue. Whereas infants can rebuild sections of lung after damage, adults can't.