Tubulogenesis: An Inside Job

Size does matter. While endlessly debated in social circles, this is unquestionably true for the normal function of the epithelial and endothelial tubes that comprise such organs as the vascular system, lung and kidney. The enlarged tubules in a polycystic kidney, for instance, literally crush the surrounding normal tubules, while narrowed blood vessels can cause ischemic tissue injuries. Surprisingly, the molecular and cellular mechanisms of tube-size regulation are poorly understood, and therapeutics to intervene in conditions such as polycystic kidney disease are non-existent. However, a flurry of papers, including those by Luschnig et al. [1] and Wang et al. [2] in this issue of Current Biology, have now defined a new mechanistic framework for understanding epithelial tube-size regulation in one of the best studied models for tubulogenesis, the Drosophila tracheal system [3]. Importantly, the combined results have implications for understanding not only tube-size control, but also the mechanisms of specialized apical secretion, the role of extracellular matrix (ECM) in controlling cell shape, and possibly conserved signaling or morphogenic roles for what has been considered an invertebrate specific oligosaccharide. The stage was set for the Wang and Luschnig papers [1,2] by recent papers from the Samakovlis, Uv, Krasnow, Casanova and Nüsslein-Volhard groups that showed that the genetically programmed tripling of the diameter of the tracheal tubes requires the formation of a transient lumenal chitin-based ants' motivational state determines so strongly which landmarks the ants use that most home-motivated ants ignore the food-ward route entirely. In a study with the two routes closer together, displaced home-motivated ants had the opportunity to choose between the routes; they then joined their homeward route in preference to the food-ward one [10]. That such a preference can be triggered by motivational state is borne out by experiments on wood ants showing that visual memories for the ant's homeward or food-ward route can be primed selectively simply according to whether or not the ant has fed [19]. The segregation of memory-use according to motivational state makes good sense. Often food-ward and homeward routes are intertwined so that an insect that did not prime memories according to motivational state might well retrieve the memory for the wrong route and so be guided in the wrong direction. Ants seem not to be misled in this way. Similarly, on our way to work we may pass the pub that we will visit on our way home. In our hurry we …