The function of tubular organs like the kidneys, lungs, and vessels of the vascular system is critically dependent on the length and diameter of the tubular branches of which they are composed. Several devastating pathological conditions like polycystic kidney disease and ischemias have been intimately linked to the aberrant sizes of tubular organs. Yet the underlying cellular and molecular mechanisms that control tube size are poorly understood, and, consequently, drugs that intervene in tubular organ disorders are lacking.

Over the past few years, the tracheal system of the fruit fly Drosophila has provided important general insights into epithelial organ morphogenesis. The fly's tracheal system is a tubular network that functions in respiration by transporting oxygen throughout the insect body. In two separate new studies, researchers have taken advantage of the usefulness of the Drosophila tracheal system as a model for understanding the development of tubular organs. Both studies point to the important role played in this process by the luminal extracellular matrix (ECM)--a scaffold of sorts that provides structure to surrounding cells and tissues. Past work had shown that inside the tracheal tube, or lumen, the polysaccharide molecule chitin forms a cylinder that is essential for the coordinated dilation of the surrounding epithelium to its normal mature size: Mutants lacking chitin show tubes with irregular diameter.

In one of the new studies, a group led by Christos Samakovlis at Stockholm University has revealed further evidence for an "instructive" function of the luminal ECM in tube size control. They found that while uniform expansion of tube diameter requires the growth of a luminal chitin scaffold, the subsequent modification of this chitinous mandrel by specialized enzymes (called chitin deacetylases) instructs the termination of tube elongation. Mutations in two genes encoding these enzymes disrupt tubular morphogenesis. The authors'
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
23-Jan-2006

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