Transcriptional cell-autonomous response to hypoxia of Drosophila tracheal cells. (A) Left panel: Photograph of a Drosophila normoxic embryo transgenic for a GFP hypoxia-inducible transcriptional reporter. The GFP reporter is not expressed in conditions of oxygen availability; the green dots indicate the position in which the reporter is expected to be expressed in hypoxia, according to the models that account for mammalian angiogenesis (i.e. in target tissues). Right panel: In embryos exposed to hypoxia, the HIF-dependent reporter is induced in tracheal cells, and not in target tissues, as would predict by the angiogenesis-born model. (B) In Drosophila larvae exposed to hypoxia, tracheal terminal cells (TTCs) generate extra-ramifications. (C) In larvae exposed to hypoxia, the sprouting response schematized in (A) does not occur in TTCs that are mutant for Sima. (D) Over-expression of Sima, specifically in tracheal cells, is sufficient to induce tracheal terminal cell (TTC) sprouting in a normoxic larva. (E) Tracheal over-expression of the FGF receptor Breathless is also sufficient to promote tracheal extra-sprouting in normoxia.