Dissertation/Thesis Abstract

Regulation of growth by TGF-β in Drosophila
by Gesualdi, Scott C., Ph.D., Florida Atlantic University, 2009, 82; 3368238
Abstract (Summary)

Key to our understanding of growth regulation in Drosophila would be discovering a ligand that could regulate steroid synthesis. Activins are involved in regulating steroid hormone release in vertebrates. In invertebrates, they most likely function to keep ecdysone levels low to allow the larvae more time to achieve critical weight in order to initiate the metamorphic process. TGF-β (Transforming Growth Factor Beta) is a family of cytokine growth factors. We find that two members of the TGF-β signaling pathway Drosophila Activin (dACT) and Activin-like ligand Dawdle (DAW) signal through the type I receptor Baboon (BABO) and the type II receptor PUNT to primarily activate the transcription factor dSMAD2 and MAD to a lesser extent. One transcription factor brinker (brk ) appears to be central to dACT signaling. In wings dACT signaling is necessary to promote growth however, dACT is not expressed in wings suggesting that dACT is provided through the endocrine system. One possible target tissue of dACT signaling is the ring gland (RG), which synthesizes and secretes the steroid hormone ecdysone (E). Consistent with this idea, using the UAS/GAL-4 system, we find that over-expression of the TGF-β ligand dACT with the neuroendocrine driver 386Y-GAL4 results in an increase in the size of flies. Surprisingly, when we increase the dose with two copies of dACT, it decreases the size of flies also indicating non-autononomous effects. We find that over-expression of the activated form of the dACT type I receptor Baboon (BABO) or brk with the ring gland specific driver phm-GAL4 results in developmental arrest of larvae that stay small and never pupate. The developmental arrest can be overcome by feeding larvae E, suggesting that dACT represses E through brk. These results suggest a model where dACT signaling activates brk which inhibits E. We picked three cytochrome P450 enzymes: phantom (PHM), disembodied (DIS) and spookier (SPKR). PHM is not regulated by any component in the dACT signaling pathway however, we find DIS and SPKR are down-regulated through brk. MAD and dSmad2 bind to a SMAD binding site and MAD out-competes dSmad2. We find no evidence that Drosophila insulin-like peptides (DILPS)/P13-Kinase or Ras signal through the dActivin signaling pathway.

Indexing (document details)
Advisor:
Commitee:
School: Florida Atlantic University
School Location: United States -- Florida
Source: DAI-B 70/08, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Molecular biology, Genetics, Cellular biology
Keywords: Activin, Ecdysone, TGF-beta
Publication Number: 3368238
ISBN: 9781109296501
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