Browsing by Subject "Activin"
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Item The activin ligand dawdle links diet and metabolism via receptor isoform-specific signaling in Drosophila.(2009-07) Jensen, Philip AnthonyAbstract not available.Item Activin signaling promotes the competence of the prothoracic gland during Drosophila metamorphosis(2010-08) Gibbens, Ying YeIn insects, the timing of metamorphosis is modulated by a large titer of the steroid hormone ecdysone produced by the prothoracic gland. However, the molecular mechanisms that control production of the ecdysone titer are not completely understood. Here we show that blocking Activin signaling in Drosophila prothoracic gland causes developmental arrest prior to metamorphosis. This defect is due to the absence of the ecdysone titer, a likely consequence of reduced expression of the ecdysone biosynthetic enzymes. We further demonstrate that Activin signaling may regulate the competence of the prothoracic gland to respond to prothoracicotropic hormone and insulin, two hormonal signals that have been shown to trigger ecdysone synthesis. These findings suggest that Activin signaling is required for insect metamorphosis by providing competence that allows tissue- and stage-specific response to metamorphic stimuli.Item Regulation of Body Size by TGF-β Signaling(2018-09) Moss-Taylor, LindsayNearly all life history traits scale with body size, imparting incredible importance on control of growth and size during animal development. Nutrition, genetic and environmental inputs influence the growth rate during development to determine final body size. These inputs are processed by the insulin/insulin-like growth factor signaling pathway (IIS), which is the major regulator of growth, and other pathways, like TGF-β, which modulate tissue growth or IIS. Mutations in the gene coding for the Drosophila TGF-β ligand Activinβ (Actβ) cause reduced final body size and accelerated growth termination. Using the Gal4/UAS system, I show Actβ is expressed in distinct cell types in the nervous system. Using rescue experiments, I show the Actβ phenotypes can be rescued by overexpression of Actβ in some, but not all, of the cell types in which it is endogenously expressed. Additionally, the growth rate of Actβ mutants is reduced, demonstrating the size phenotype is not simply due to early growth termination from precocious timing. Muscle-specific knockdown of the TGF-β signaling transducer/transcription factor dSmad2 also reduces body size, identifying muscle is a target tissue of the Actβ signal. The change in body size is due to a reduction in the size of skeletal muscles, not a systemic reduction in size. Autophagy markers are upregulated in Actβ mutants but, surprisingly, overexpression of autophagy regulators does not rescue the Actβ size phenotype, indicating Actβ regulation of autophagy is TOR-independent. These results provide new insights into mechanisms of body size and muscle size control during animal development. This thesis details the functions of Actβ in the regulation of body size and developmental timing. Chapter 2 describes the study of how Actβ controls body size and developmental timing. Chapter 3 investigates the roles of Actβ in regulating metabolism and IIS.Item Timing, growth and homeostasis: an anthology of three novel players in Drosophila melanogaster(2013-08) Ghosh, ArpanDevelopmental timing, growth and homeostasis form the cornerstones that shape the genesis and subsequent maintenance of a healthy adult for all multicellular organisms. Understanding the mechanisms that regulate these processes has important implications both from the perspective of our understanding of basic biology and also for our understanding of complex biological disorders involving these processes. My work explores the mechanisms regulating developmental timing, homeostasis and growth using the model organism Drosophila melanogaster. In this thesis I report involvement of three novel players in the regulation of timing, homeostasis and growth in the Drosophila larvae.Firstly, my work unearths the mechanism by which the developmental gap gene, giant, regulates developmental timing in Drosophila larvae. While the effect of Giant (Gt) on larval developmental timing was long known, the mechanism by which Gt exerted this effect was not known. I find that Gt affects developmental timing by influencing the developmental fate of the prothoracicotropic hormone producing PG neurons that are essential for determining the timing of larval developmental transitions. Additionally, I show that Gt is required for PG neuron axon targeting. Secondly, I show that TGF-beta/Activin signaling mediated by the Activin-like ligand Dawdle (Daw) regulates sugar homeostasis, pH balance and mitochondrial metabolism in Drosophila larvae. Canonical signaling by Daw regulates sugar homeostasis primarily by affecting release of insulin in the larvae. The effect of Daw on pH is mediated independently by Daw's action on mitochondrial metabolism and production of metabolic acids. Interestingly, Daw affects both phenotypes in a dose-dependent manner, as demonstrated by both loss-of-function and over-expression/gain-of-function experiments, thereby providing evidence for a hormonal role of Daw in regulating systemic homeostasis. Lastly, I show that eukaryotic uracil salvaging enzyme uracil phospho-ribosyltransferase (UPRT), that was considered inactive in higher eukaryotes including Drosophila, is active in the Drosophila larvae. The Drosophila UPRT homologue, Krishah, can actively incorporate a uracil derivative (4TU) into RNA indicating that the enzyme is active in vivo. Interestingly, I find that Krishah is also essential for larval growth as knocking out the gene leads to impaired larval growth and increased larval and pupal lethality.