Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780645
Title: Sex, signalling, and steroids : regulation of nuclear size and intracellular trafficking in secondary cells in the D. melanogaster male accessory gland
Author: Hellberg, Josephine E. E. U.
ISNI:       0000 0004 7966 2866
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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Abstract:
The fruit fly, Drosophila melanogaster, can be a useful in vivo model for understanding the biology of cells and the signalling pathways by which this biology is regulated. My Dissertation focuses on the accessory glands of male D. melanogaster, where two types of cells-main cells and secondary cells-are responsible for producing many seminal fluid proteins. The work presented in this Dissertation describes some of the aspects of secondary cell biology that are involved in controlling the growth and secretory activity of these cells. Secondary cells are secretory cells, and they contain large intracellular compartments-some of which accumulate proteins destined for secretion. The BMP ligand, Decapentaplegic (Dpp), is one such protein, which can regulate secondary cell biology via an autocrine signalling mechanism. Previous work has shown that BMP signalling regulates a D. melanogaster steroid receptor-the ecdysone receptor (EcR)-to form a BMP/EcR signalling axis that controls secondary cell nuclear growth. In this Dissertation, I show that the BMP/EcR signalling axis regulates the expression of the D. melanogaster initiator caspase, DRONC, and that this caspase and other related regulators control intracellular trafficking in secondary cells. I propose that this process might be orchestrated via non-apoptotic mobilisation of the cytoskeleton. In addition, I show that secondary cells produce the lipoprotein, Hedgehog, and that it is released into the seminal fluid. Like Dpp, Hedgehog seems to signal back into secondary cells to regulate their biology and nuclear growth. This growth is reduced when hedgehog (and its downstream signalling components) is knocked-down in secondary cells. Conversely, activating the Hedgehog-dependent transcription factor, Cubitus interruptus (Ci), promotes this growth. Like BMP signalling, autocrine Hedgehog signalling might play an important role in coordinating growth and secretion in secondary cells. Previous studies have shown that secondary cell nuclei grow after mating. In an effort to understand how this growth is regulated, I identified the BMP/EcR signalling axis as a key regulator-alongside cell cycle regulators, like Cyclin D and Cyclin E. My work shows that secondary cell nuclei seem to grow after mating, partly as the result of BMP/EcR-dependent increases of the secondary cell DNA content-perhaps to increase the cells' biosynthetic potential. This suggests that secondary cell nuclei can grow via two distinct mechanisms: one that is mating-dependent, and one that is not. Altogether, the work presented in this Dissertation describes important roles for steroid signalling and sexual activity in the regulation of secondary cell biology. This complex co-ordination of BMP- and steroid signalling might also be relevant to other organisms.
Supervisor: Wilson, Clive Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.780645  DOI: Not available
Keywords: reproductive biology ; cell biology ; Drosophila melanogaster
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