Organ development in the embryo requires precise coordination and timing of cell growth in three-dimensional space to produce the correct anatomic form and shape. Researchers at Children's Hospital Boston, led by Dr. Donald Ingber, a senior researcher in the Vascular Biology Program, have demonstrated that the process of budding and branching in the developing lung is driven by mechanical forces generated within individual cells. They have also identified a possible biochemical target for intervention. These insights could lead to new ways to prevent, minimize or even correct diseases and anomalies of the lungs, which are common in premature newborns.

Previously, Ingber and colleagues have shown that epithelial tissues the thin cell layers that line organs and other body structures, including the lung's airways -- take their characteristic three-dimensional forms through differences in cell growth in different spatial locations. This cell growth is influenced by changes in the extracellular matrix, the flexible, egg-carton-like structure that surrounds and supports cells. Cells are physically connected to the matrix via their cytoskeleton, an internal scaffolding of crisscrossing fibers and tubes that generates tensional forces like those in muscle. Through these tensed connections, cells can "feel" mechanical forces that push and pull on the tissue they are in. If they feel a stretch, cells will begin to proliferate; if they feel compressed, they stop growing and may begin to die off. The parts of the tissue with greater cell growth expand more rapidly than the surrounding areas, causing buds and branches to form.

In this new paper, published in the February 2005 issue of Developmental Dynamics, Ingber and colleagues manipulated the mechanical force felt by developing mouse lungs by modulating the activity of a cellular signaling enzyme called Rho. Rho facilitates a chemical reaction that causes contraction of fibers in the cytoskeleton, i
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Contact: Susan Craig
susan.craig@childrens.harvard.edu
617-355-6420
Children's Hospital Boston
17-Feb-2005

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