Fibronectin for branching

Branched organs are shaped when epithelia make their own paths, according to a study by Takayoshi Sakai, Melinda Larsen, and Kenneth Yamada (National Institutes of Health, Bethesda, MD). The pathmaker in this process is fibronectin (FN), which tells cells to let go of their neighbors and instead grab hold of the underlying matrix.

Organs such as the lung and kidney gain surface area by forming numerous branches, which are generated by cycles of budding and cleft formation in epithelial cells. Branching is known to involve growth factor–regulated interactions between the epithelium and mesenchyme, but the authors wanted to know how individual cells respond during branching. Using the developing mouse salivary gland as a model, the group now reports that epithelia change their architecture by secreting FN fibrils in newly forming clefts.

Although cleft-initiating signals are not yet known, cleft formation was induced by FN expression in cells bordering the cleft. Inhibition of FN mRNA expression in the epithelium or antibody inhibition of FN or its integrin receptor inhibited branching and cleft formation. In contrast, exogenous expression of FN induced excess branching in cultured salivary glands. FN fibrils suppressed local levels of the cell–cell adhesion molecule cadherin in nearby epithelial cells. Cadherin loss, which occurs via both local redistribution and mRNA suppression, probably releases the epithelial cells from each other as they attach to the matrix FN.

Lung and kidney epithelia also have cleft FN pools that function as in salivary glands, suggesting that FN is widely used for branching. “We wonder whether this kind of local developmentally regulated appearance of fibronectin is possibly a general strategy in tissue remodeling,” says Yamada. ▪

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