Blood Vessels Play Critical Role in Lung Development

A new study elucidates the role of blood vessels in guiding early lung development, especially in the essential, highly reproducible branching pattern of bronchial airways.

Researchers at The Saban Research Institute (SRI) of the Children's Hospital Los Angeles (CHLA; CA, USA) and the Hebrew University (Jerusalem, Israel) employed a computer-based three-dimensional (3D) reconstruction technique to view lung tissue and its growth processes at work. They discovered that blood vessels in the lung not only perfuse the tissues with nutrients and oxygen, they also determine the 3D branching pattern of the airways and the development of the lining of the lung's airways and capillaries. The resulting coordinated branching of the bronchi and blood capillaries culminate in their coalignment in the mature lung.

The researchers also found that when they blocked the signaling mechanism that controls the formation of capillaries, key elements of the alignment process no longer took place. While two-dimensional (2D) epithelial branching continued at a nearly normal rate, there was a marked overall reduction in the number of branching events. Most importantly, branching processes failed that would normally be needed to rotate the branching process into the third dimension, essential to developing a 3D organ; this role of the vasculature was independent of perfusion, blood flow, or blood-borne substances.

The researchers identified one reason for the defect in 3D airway branching--a disturbance in the distribution of specific growth factor signals. Inhibition of the normal branching sequence could be explained in part by disturbing the unique spatial expression pattern of the key branching mediator FGF10, and by misregulated expression of the branching regulators Shh and sprouty2. Significantly, restoration of vascularization fully rescued arrested airway branching and restored normal lung size and 3D architecture. The study was published in the June 2011 issue of Development.

"We've discovered some important things about how the airways talk to the capillaries through growth factors provided by the epithelium," said lead author David Warburton, DSc, MD, director of developmental biology and regenerative medicine at the SRI. "But precisely how the capillaries talk to the airways remains an open question. The ultimate objective of this research is to make new lung tissue for people who need it."

Related Links:
Children's Hospital Los Angeles
Hebrew University