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Children's Hospital Boston researchers, led by Donald Ingber, MD, PhD, in the Vascular Biology Program, have shown that the process of budding and branching in the developing lung is driven by mechanical forces generated in cells, and that these can be modulated chemically. Their findings could spawn new ways to prevent, minimize or even correct the lung diseases and anomalies that so commonly afflict premature babies.
Previously, Ingber showed that cells "feel" outside mechanical forces at points where their cytoskeleton, an internal scaffolding, connects to the flexible supportive tissue surrounding cells called the extracellular matrix. If cells feel stretched, their growth increases; if compressed, cells stop growing and may die. In this new study (Developmental Dynamics, Feb. 2005), Ingber and colleagues manipulated the stretch felt by developing mouse lungs by stimulating or inhibiting an enzyme called Rho, which causes fibers in the cytoskeleton to contract.
Left alone, mouse lungs formed buds that enlarged until a cleft formed in their tip, pinching them into two or three new buds. But when lungs were treated with Rho inhibitors, relaxing the cytoskeleton, bud formation was reduced by more than half. Rho activators promoted cytoskeletal contraction, increasing the stretch and speeding bud formation. Tinkering with Rho also affected the development of nearby capillaries, which grow along with lung tissue to form a functional organ.