Novel mechanisms of tube-size regulation revealed by the Drosophila trachea

Abstract

The size of various tubes within tubular organs such as the lung, vascular system and kidney must be finely tuned for the optimal delivery of gases, nutrients, waste and cells within the entire organism. Aberrant tube sizes lead to devastating human illnesses, such as polycystic kidney disease, fibrocystic breast disease, pancreatic cystic neoplasm and thyroid nodules. However, the underlying mechanisms that are responsible for tube-size regulation have yet to be fully understood. Therefore, no effective treatments are available for disorders caused by tube-size defects. Recently, the Drosophila tracheal system has emerged as an excellent in vivo model to explore the fundamental mechanisms of tube-size regulation. Here, we discuss the role of the apical luminal matrix, cell polarity and signaling pathways in regulating tube size in Drosophila trachea. Previous studies of the Drosophila tracheal system have provided general insights into epithelial tube morphogenesis. Mechanisms that regulate tube size in Drosophila trachea could be well conserved in mammalian tubular organs. This knowledge should greatly aid our understanding of tubular organogenesis in vertebrates and potentially lead to new avenues for the treatment of human disease caused by tube-size defects.

R3 receptor tyrosine phosphatases: Conserved regulators of receptor tyrosine kinase signaling and tubular organ development

“…The seamless tubes are intracellular structures that form within terminal cells. Many genes have been identified that affect the formation and morphology of tracheal tubes (reviewed by (Affolter and Caussinus, 2008; Caviglia and Luschnig, 2014; Schottenfeld et al, 2010; Zuo et al, 2013). …”

Book lung development in the embryo, postembryo and first instar of the cobweb spider, Parasteatoda tepidariorum C. L Koch, 1841 (Araneomorphae, Theridiidae)

“…Especially emphasized are the cellular mechanisms and genetics for tube development and maturation (increasing diameter and length, branching and clearing) in the trachea of Drosophila and other tubular structures such as those in the kidney, lungs and circulatory system (Fristrom, 1988;Andrew and Ewald, 2010;Zuo et al, 2013). The results herein provide additional information for book gills and book lungs as models for research on the physical, molecular and structural basis for the cellular formation of the lumen and walls of channels and tubules.…”

“…Channel width expansion in spider book lungs probably results from vesicle release into the channel lumen (Figs. 10, 11, 12B, 13A) as in tracheal expansion in Drosophila (F€ orster et al, 2010;Zuo et al, 2013). Channel lengthening in book lungs may involve some of the same cellular mechanisms as in tube lengthening: cell proliferation, recruitment and positioning (Andrew and Ewald, 2010).…”

Time to make the doughnuts: Building and shaping seamless tubes

“…2B, C), but is then cleared during cuticle maturation (reviewed in [86, 87]). Mutants for Expansion, a gene required for chitin deposition, revealed large luminal dilations in terminal cells, but not fusion cells, suggesting differential importance of the luminal ECM in shaping these two seamless tube types [97, 98].…”

“…PAR proteins recruit the exocyst complex for vesicle docking [48]. A chitin rod determines lumen diameter [86, 87, 97, 98]. The ZP proteins Dumpy (Dpy) and Piopio (Pio) may link the chitin rod to the apical membrane and cytoskeleton [60, 93–95].…”