Abstract: Drosophila trachea is a premier model to study tube morphogenesis. After the formation of continuous tubes, tube maturation follows. Tracheal tube maturation starts with an apical secretion pulse that deposits extracellular matrix components to form a chitin-based apical luminal matrix (aECM). This aECM is then cleared and followed by the maturation of taenidial folds. Finally, air fills the tubes. Meanwhile, the cellular junctions are maintained to ensure tube integrity. Previous research has identified several key components (ER, Golgi, several endosomes) of protein trafficking pathways that regulate the secretion and clearance of aECM, and the maintenance of cellular junctions. The Osiris (Osi) gene family is located at the Triplo-lethal (Tpl) locus on chromosome 3R 83D4-E3 and exhibits dosage sensitivity. Here, we show that three Osi genes (Osi9, Osi15, Osi19), function redundantly to regulate adherens junction (AJ) maintenance, luminal clearance, taenidial fold formation, tube morphology, and air filling during tube maturation. The localization of Osi proteins in endosomes (Rab7-containing late endosomes, Rab11-containing recycling endosomes, Lamp-containing lysosomes) and the reduction of these endosomes in Osi mutants suggest the possible role of Osi genes in tube maturation through endosome-mediated trafficking. We analyzed tube maturation in zygotic rab11 and rab7 mutants, respectively, to determine whether endosome-mediated trafficking is required. Interestingly, similar tube maturation defects were observed in rab11 but not in rab7 mutants, suggesting the involvement of Rab11-mediated trafficking, but not Rab7-mediated trafficking, in this process. To investigate whether Osi genes regulate tube maturation primarily through the maintenance of Rab11-containing endosomes, we overexpressed rab11 in Osi mutant trachea. Surprisingly, no obvious rescue was observed. Thus, increasing endosome numbers is not sufficient to rescue tube maturation defects in Osi mutants. These results suggest that Osi genes regulate other aspects of endosome-mediated trafficking, or regulate an unknown mechanism that converges or acts in parallel with Rab11-mediated trafficking during tube maturation. Author summary: The Drosophila trachea is the ideal model system to study conserved and fundamental mechanisms of tubular organ formation. In humans, tubular organs include, but are not limited to, the lungs, kidneys, and blood vessels. Defects in tube formation cause severe human diseases, such as polycystic kidney disease. After tubes begin to form, they will continue to mature to their functional lengths and diameters, and in the case of tracheae and lungs, will fill with air. The protein trafficking pathway, which is involved in delivering proteins to their final destinations, is heavily involved in various steps of the tube formation process. Previous studies have identified several key components within the protein trafficking pathway (ER, Golgi, endosomes) that regulate various processes during tube maturation. We identified the Osiris proteins, which are required for tube maturation including the maintenance of cellular junctions, clearance of the apical lumen, formation of taenidial folds to prevent the collapse of the tube, and air filling. In addition, Osi proteins regulate tube maturation potentially through endosome-mediated trafficking. This work will improve our understanding of the function of Osi genes and vesicular trafficking in the tube maturation process. [ABSTRACT FROM AUTHOR]
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