The viability of complex organisms is dependent upon the maintenance of oxygen homeostasis. In Drosophila this is accomplished by the development of the tracheal system, a branched oxygen-conducting network, and by the ability of cells to sense and respond to conditions of lowered oxygen availability, or hypoxia. This hypoxic response is based on the transcriptional activity of the Hypoxia induced factor (HIF) which is conserved from Drosophila to humans. Here we describe novel functions of the Drosophila tumor suppressor homolog archipelago (ago) in regulating oxygen homeostasis via roles in tracheogenesis and in restricting the hypoxic response.
ago mutant embryos display defects in tracheal development due to deregulated activity of the Trachealess transcription factor, illustrating a key regulatory role for ago in the development of the oxygen delivery system. In addition to this developmental role, ago also controls the response to hypoxia in larval and adult Drosophila by regulating the activity of Drosophila HIF. Deregulation of dHIF in ago mutants uncouples activation of the hypoxic response from oxygen deprivation, leading to its ectopic induction in normoxia and altering the organismal response to oxygen deprivation. These findings identify ago as a member of a novel HIF regulatory pathway.
|Advisor:||Moberg, Kenneth H.|
|Commitee:||Faundez, Victor G., Kelly, William G., Lucchesi, John G., Shepherd, Iain G.|
|Department:||Biological and Biomedical Sciences|
|School Location:||United States -- Georgia|
|Source:||DAI-B 70/07, Dissertation Abstracts International|
|Keywords:||Drosophila, Hypoxic response, Oxygen homeostasis, Tracheogenesis|
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