Stress stunts organ growth

Organ size is controlled by a combination of morphogens and mechanical stress, propose Lars Hufnagel, Boris Shraiman (University of California, Santa Barbara, CA), and colleagues. Morphogen gradients, they show, are not sufficient to prevent overgrowth.

The popular gradient model proposes that differences in morphogen concentration across an organ are sensed by individual cells, which respond by proliferating. As a tissue grows, this gradient flattens until it no longer prods division. But Shraiman and colleagues now show that a morphogen's gradient does not change with organ size.

In the developing fly wing, the Dpp morphogen is made in a central stripe, and its concentration decays outward in both directions. By comparing fly larvae at various developmental stages, the group shows that this concentration pattern depends mainly on its diffusion and decay rates and is the same in wings of all sizes.

The authors instead propose that cells near the edge stop dividing when they get too far away and thus receive insufficient morphogen. They then needed to explain how the central cells know to stop proliferating at the same time as the outer cells. “I'm a physicist,” says Shraiman. “And to a physicist, mechanical stress is a very natural thought.”

The supposed stress comes from differences in growth rates. As neighboring cells are tightly joined by adherens junctions and thus cannot change position, proliferating cells in the center are getting crushed, while the outer quiescent cells are being stretched.

Computational modeling suggests that mechanical stress negatively feeding back on morphogen-induced growth can account for size control. Now the group needs to test their model and find the stress detectors. Molecules such as β-catenin that link the cytoskeleton to adherens junctions and also induce gene expression are some of their favored candidates.

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