Drosophila archipelago regulates oxygen homeostasis via novel roles in tracheogenesis and the hypoxic response Open Access

Mortimer, Nathan T (2009)

Permanent URL: https://etd.library.emory.edu/concern/etds/pz50gw351?locale=en
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Abstract

Drosophila archipelago regulates oxygen homeostasis via novel roles in
tracheogenesis and the hypoxic response
By Nathan T. Mortimer
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.

Table of Contents

Table of Contents
Chapter 1. Oxygen homeostasis




Page 1
1.A. Introduction






Page 2
1.B. The Drosophila tracheal system: a conserved oxygen-
conducting organ





Page 5
1.C. A conserved mechanism for sensing and responding to
hypoxia







Page 23
1.D. Hypoxia and HIF signaling in oxygen homeostasis,
development and disease




Page 29
1.E. Non-canonical regulation of HIF signaling by tumor
suppressor proteins





Page 40
1.F. Purpose







Page 44
Chapter 2. The Drosophila F-box protein Archipelago controls levels of the
Trachealess transcription factor in the embryonic tracheal system










Page 46
2.A. Introduction






Page 47
2.B. ago has a role in embryonic tracheal development

Page 51
2.C. ago acts upstream of trachealess and breathless

Page 64
2.D. Ago binds Trh and restricts Trh levels in cells

Page 73
2.E. Discussion of results





Page 78
Chapter 3. Regulation of Drosophila embryonic tracheogenesis by dVHL
and hypoxia







Page 84
3.A. Introduction






Page 85

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