Tissue-Specific Responses from a Global Developmental Signal: A Detailed Subcellular Analysis of the 20E and Rab Signaling Pathways Controlling Exocrine Secretion During Drosophila Development

During metamorphosis, the steroid hormone 20-hydroxecydysone (20E) triggers a plethora of tissue-specific responses in the common fruit fly, Drosophila melanogaster. The salivary glands are exocrine organs that respond to a large pulse of 20E to secrete a massive cargo of stored glycoproteins called glue. Because the glands are amenable to ex vivo-organ culture and powerful genetic manipulations, they are an excellent model for studying the conserved developmental and physiological signaling pathways that regulate the general function of these specialized secretory tissues. Our lab has generated transgenic animals in which the secreted glue molecules are tagged with fluorescent proteins. I have used these flies to characterize the number, size, shape, and relative pH of the secretory cargoes in live cells before and after exposure to the 20E steroid hormone. Using a specialized binary-expression system, I have complemented this analysis to characterize cells that have been specifically compromised for molecules that control this steroid-regulated secretion pathway. Here, I report how genetically manipulating 20E exposure, reception, transcription factor induction, and activation of Rab GTPases affects the maturation, transport, and release of the glue cargoes. Because humans and flies often use the same signaling molecules and pathways in their tissue-specific responses to steroids, this thesis is expected to contribute to our fundamental knowledge of how exocrine tissues respond to steroids and secrete cargoes into a limited luminal space before expulsion to the outside of the animal