A study of the molecular and cell biological processes of tracheal tube formation and maintenance in Drosophila melanogaster

Many organs are composed of epithelial tubes that transport vital fluids. Such tubular organs develop in many different ways and generate tubes of widely varying sizes and structures, but always with the apical epithelial surface lining the lumen. Recent progress in diverse cell culture and genetic models of tube morphogenesis suggest apical membrane biogenesis, vesicle fusion, and secretion play central roles in tube formation and growth, allowing for the conceptualization of a unifying mechanism of tube morphogenesis that has been modified to create tube diversity. Furthermore, there is evidence that defects in the tube size sensing step can lead to human polycystic kidney disease.; Dramatic tube expansion is a required step during the development of epithelial tube networks, yet little is known about the genetic and cellular processes involved in tube expansion and maintenance. Herein is presented a genetic, cellular, and ultrastructural analysis of cystic, a gene required for the proper expansion and maintenance of Drosophila tracheal tubes. cystic mutations form an allelic series that can be divided into four classes of increasing phenotypic severity. In the most severe (presumptive amorphic) mutants, apicobasal polarity of the tracheal epithelium is established normally and trachea branch and form a lumen, however subsequent expression of tube expansion markers and the apically localized Discs-lost protein are reduced or altered and, at the time the tubes normally expand uniformly, they instead develop irregular expansions and constrictions along their length. Ultrastructural studies indicate that the tracheal epithelium is intact and apical cuticle secretion initiates normally during expansion, but subsequent cuticle development is arrested and the mutants never form the thick procuticle layer and taenidial folds characteristic of mature tracheal cuticle. These results suggest that cystic is required for maturation of the apical tracheal surface and tracheal cuticle, which we propose stabilizes lumen structure during tube expansion. Genetic mosaic analysis indicates that the gene functions cell non-autonomously, so cystic may be involved in the production of a secreted signal or luminal constituent.