Sec24-Dependent Secretion Drives Cell-Autonomous Expansion of Tracheal Tubes in Drosophila

Abstract

Epithelial tubes in developing organs, such as mammalian lungs and insect tracheae, need to expand their initially narrow lumina to attain their final, functional dimensions. Despite its critical role for organ function, the cellular mechanism of tube expansion remains unclear. Tracheal tube expansion in Drosophila involves apical secretion and deposition of a luminal matrix, but the mechanistic role of secretion and the nature of forces involved in the process were not previously clear. Here we address the roles of cell-intrinsic and extrinsic processes in tracheal tube expansion. We identify mutations in the sec24 gene stenosis, encoding a cargo-binding subunit of the COPII complex. Via genetic-mosaic analyses, we show that stenosis-dependent secretion drives tube expansion in a cell-autonomous fashion. Strikingly, single cells autonomously adjust both tube diameter and length by implementing a sequence of events including apical membrane growth, cell flattening, and taenidial cuticle formation. Known luminal components are not required for this process. Thus, a cell-intrinsic program, rather than nonautonomous extrinsic cues, controls the dimensions of tracheal tubes. These results indicate a critical role of membrane-associated proteins in the process and imply a mechanism that coordinates autonomous behaviors of individual cells within epithelial structures.

Luminal matrices: An inside view on organ morphogenesis

“…For instance, the addition of apical membrane to accommodate rapid lumen diameter expansion can be driven by exocytosis, as in the Drosophila tracheae [1,2], or by reshuffling of intracellular membrane to the apical surface, as in the excretory organ in C. elegans [3]. Oriented cell intercalation, cell division and cell elongation also participate in regulating lumen dimensions during size-maturation of the organ.…”

“…2A). During this period, new apical membrane is added through apical secretion, and animals with impaired secretion fail to expand the tracheal lumen while completing many other morphogenetic processes [1,2]. Tracheal tube elongation is controlled independently of diametric expansion and requires the tyrosine kinase Src42 for polarized cell shape changes in the axial dimension of the tubes [4,5].…”

“…In case of the embryonic tracheal tubes, diametric growth of the lumen is driven by secretion to increase the apical cell surface area [1]. Yet, genes involved in chitin synthesis and chitin organization are essential for uniform diameter expansion.…”

A novel Cre/loxP system for mosaic gene expression in the Drosophila embryo

“…The Flip-out Gal4 system was previously used in Drosophila to induce mosaic gene expression in the tracheal system during embryogenesis, by driving FLP expression under a heat-shock promoter, i.e., hs-FLP (Ribeiro et al, 2004;F€ orster et al, 2010). However, we hardly detected any Gal4 -dependent mosaic expression of UAS-RFP in early embryos using the conditions described previously (Fig.…”

“…The mosaic expression of Gal4 using the Flip-out Gal4 system was induced under two different conditions, as described previously (Ribeiro et al, 2004;F€ orster et al, 2010).…”