Remodelling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis in Drosophila

The Drosophila trachea, as the functional equivalent of mammalian blood vessels, senses hypoxia and oxygenates the body. Here, we show that the adult intestinal tracheae are dynamic and respond to enteric infection, oxidative agents and tumours with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated regeneration and is sufficient to drive ISC proliferation in undamaged intestines. Gut damage or tumours induce HIF-1α (Sima in Drosophila ), which stimulates tracheole branching via the FGF (Branchless (Bnl))–FGFR (Breathless (Btl)) signalling cascade. Bnl–Btl signalling is required in the intestinal epithelium and the trachea for efficient damage-induced tracheal remodelling and ISC proliferation. Chemical or Pseudomonas- generated reactive oxygen species directly affect the trachea and are necessary for branching and intestinal regeneration. Similarly, tracheole branching and the resulting increase in oxygenation are essential for intestinal tumour growth. We have identified a mechanism of tracheal–intestinal tissue communication, whereby damage and tumours induce neo-tracheogenesis in Drosophila , a process reminiscent of cancer-induced neoangiogenesis in mammals. Tamamouna, Rahman et al. show that midgut-associated tracheae in Drosophila increase their branching in response to infection, oxidative stress and tumours, driving intestinal regeneration as well as tumour growth.