Keeping biological tubes in check: New insights into tube size morphogenesisThe 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' additional discovery that proper luminal localization of one of the chitin deacetylases requires a specialized secretory pathway and intact structures called paracellular septate junctions provides a mechanistic model for tracheal tube size regulation.
The other new study, from Stefan Luschnig and colleagues at Bayreuth University, Germany, and at Stanford University, reports a similar set of findings. These researchers also identified the two chitin deacetyase genes as specifically controlling tube length. As did the Samakovlis group, the researchers found that mutations in these genes, called serpentine (serp) and vermiform (verm), cause excessively elongated and tortuous tracheal tubes. Unlike previously characterized genes, serp and verm are not required for producing chitin, but rather are required for its normal fibrillar structure. The findings of the two groups suggest that tube length is controlled by modulating physical properties of the chitin cylinder. These properties may be sensed by tracheal cells, mediating the restriction of cell elongation.
Given the many similarities in the developmental mechanisms and cellular designs of tubular organs across species, the distinct roles of the luminal ECM in tracheal tube size control provide new leads in the investigation of lumen size regulation in a variety of tubular organs.
The researchers include Stefan Luschnig of the University of Bayreuth in Bayreuth, Germany, Howard Hughes Medical Institute, and Stanford University School of Medicine in Stanford, CA; Tilmann Batz and Kristina Armbruster of the University of Bayreuth in Bayreuth, Germany; Mark A. Krasnow of the Howard Hughes Medical Institute and Stanford University School of Medicine in Stanford, CA. Shenqiu Wang, Satish Arcot Jayaram, Johanna Hemphala, Kirsten-Andre Senti, Vasilios Tsarouhas, Haining Jin, and Christos Samakovlis of Stockholm University in Stockhom, Sweden. This work was supported by grants from VR, SSF, and WCN to C.S. S.L. was supported by long-term fellowships from the European Molecular Biology Organization and the Human Frontier Science Program Organization and is grateful to Christian Lehner for support at the University of Bayreuth. M.A.K. is an Investigator of the Howard Hughes Medical Institute.
Luschnig et al.: "serpentine and vermiform Encode Matrix Proteins with Chitin Binding and Deacetylation Domains that Limit Tracheal Tube Length in Drosophila." Current Biology 16, 186–194, January 24, 2006 DOI 10.1016/j.cub.2005.11.072 www.current-biology.com
Wang et al.: "Septate-Junction-Dependent Luminal Deposition of Chitin Deacetylases Restricts Tube Elongation in the Drosophila Trachea." Current Biology 16, pages 180–185, January 24, 2006 DOI 10.1016/j.cub.2005.11.074 www.current-biology.com
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