Development and Function of the Drosophila Tracheal System

Abstract

The tracheal system of insects is a network of epithelial tubules that functions as a respiratory organ to supply oxygen to various target organs. Target-derived signaling inputs regulate stereotyped modes of cell specification, branching morphogenesis, and collective cell migration in the embryonic stage. In the postembryonic stages, the same set of signaling pathways controls highly plastic regulation of size increase and pattern elaboration during larval stages, and cell proliferation and reprograming during metamorphosis. Tracheal tube morphogenesis is also regulated by physicochemical interaction of the cell and apical extracellular matrix to regulate optimal geometry suitable for air flow. The trachea system senses both the external oxygen level and the metabolic activity of internal organs, and helps organismal adaptation to changes in environmental oxygen level. Cellular and molecular mechanisms underlying the high plasticity of tracheal development and physiology uncovered through research on Drosophila are discussed.

Keywords: FlyBook; branching; development; physiology; trachea; tubulogenesis.

Figure 1

Embryonic tracheal development. (A) Tracheal placodes are specified in stage 10 and invaginate to form 10 pairs of primordia undergoing primary branching in stage 11. (B) Stage 14 embryos undergoing dorsal trunk branch fusion. (C) Trace of the tracheal system in a stage 16 embryo labeled with markers for nuclei (green spheres) and lumen (light brown). DT (dorsal trunk) is a longitudinal large-diameter tube connected to a posterior spiracle opening at the posterior end. LT (lateral trunk) is another longitudinal tube with smaller diameter. Dorsal branch (DB) 1, 5 and 9 are labeled. Note that the number of nuclei contributing to each DB is different (seven cells for DB5 and four cells for DB9). DB10 is out of focus of the original image. (D) Schematic of tracheal placode invagination. Left: during slow phase, cells in the central area of tracheal placode sharply constrict their apices to form the tracheal pit. Right: after rapid invagination, tracheal cells are fully internalized. (E) Primary branches in stage 12. Internalized tracheal primordia form stereotyped primary branches labeled DB, DTa (dorsal trunk anterior), DTp (dorsal trunk posterior), VB (visceral branch), LTa (lateral trunk anterior), LTp (lateral trunk posterior), and GB (ganglionic branch). SP (spiracular branch) is the remnant of tracheal invagination and connects the epidermal surface to the rest of the tracheal cells. (A and B) are taken from a time-lapse confocal movie of a btl-Gal4 UAS-GFP-moesin embryo (available in https://www.youtube.com/watch?v=agW1gYCz-Yo). Anterior: left, dorsal: up.

Figure 2

Cell specification and cell rearrangement during branching morphogenesis. (A) Schematic image of stage 11 tracheal primordia undergoing primary branching. Bnl/FGF (blue ovals) is expressed by groups of cells near invaginated tracheal primordia and activates Btl/FGFR and ERK activity in tracheal cells. One cell near the source of Bnl/FGF elevates Delta expression and ERK activity to the highest level and becomes a tip cell (red circle), and stimulates Notch signaling in the rest of the cells to reduce Delta expression and ERK activity to become stalk cells. Tip cells become motile and track Bnl/FGF to elongate tubules. VB (visceral branch) is not shown in this picture for clarity. (B) Schematic image of a stage 14 DB (dorsal branch) at the beginning of secondary branching. Under the influence of Wg, tip cells turn on Esg and other genes to acquire FC (fusion cell) fate (cell number 2). Esg turns off ERK signaling and permits activation of ERK signaling in the neighboring number 1 cell, which acquires TC (terminal cell) fate by activating ERK and SRF (serum response factor) gene expression. Other cells (numbers 3–7) turn on Anterior open (Aop) expression, turn off ERK, Esg, and SRF, and turn off FC and TC fate. In this stage, all cell interfaces are formed between different cells (adherens junction marked with blue, red, and green lines). One typical cell configuration is shown. Other configurations are possible. (C) Schematic image of stage 15 dorsal branch before anastomosis formation. Terminal cells (number 1) extend long cellular extension to ventral direction. Fusion cells (number 2) migrate dorsally. Stalk cells intercalate with each other (example: number 4 cell in stage 14 intercalated between cells numbered 3 and 5) and form an autocellular junction. DTa, dorsal trunk anterior; DTp, dorsal trunk posterior; GB, ganglionic branch; LTa, lateral trunk anterior; LTp, lateral trunk posterior.