Oxygen is essential for life. Aquatic ancestral animal species are thought to have independently terrestrialized and invented distinct strategies for efficient oxygen supply. The respiratory system of vertebrates like us is composed of lungs connected to the vasculature while insects have a single system delivering air directly to internal tissues. In spite of their different evolutionary histories, the formation of these different tubular networks is thought to share many cellular, genetic and molecular principles. Here, in register with preceding studies, I briefly introduce the projects of my co-authors and me, addressing several new aspects of specification and differentiation of the Drosophila airways.

The airway primordia are specified at the lateral ectoderm of each side of the embryo as 10 groups of epithelial cells. These cells coordinately invaginate from the 2-dimensional (2D) ectodermal sheet to form 3D primitive tubes. The most proximal cells to the epidermis take the pluripotent cell fate and later generate most of the pupal and adult airways. Distal cells ramify to establish the primary branches and some neighboring branches fuse, interconnecting the network. Establishing these basic architectures, the tubular network matures into functional airways, attaining proper tube sizes in diameter and length, producing an annular-ridged lining of exoskeleton to avoid tube collapse and finally filling the system with gas.

First, I present airway-promoting functions of factors that were previously assigned to repress the airway fate. Then, I present genetic frameworks discriminating between 3 ground cell fates and the more derived cell fates: A) the proximal pluripotent cells vs. the distal more differentiated cells, B) the visceral branch vs. the signal-induced primary branches and C) the 1^st metamere vs. the more posterior metameres. Lastly, I present our efforts to identify genes converting the airway tubes into a functional respiratory system.