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Title: The regulation of Drosophila ovarian germline stem cell identity by BMP signalling
Author: Wilcockson, Scott
ISNI:       0000 0004 8504 9144
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2019
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In the Drosophila ovarian germline, BMP ligands secreted by a small population of niche cells maintain germline stem cell (GSC) identity. This self-renewal signal is maintained at exquisite short range in order to ensure that upon exiting the niche, GSC daughters are able to undergo differentiation. Despite the essential role of BMP in GSC identity, very little is known of the network downstream of BMP signalling in this context. One key function is the transcriptional repression of the differentiation promoting factor bag of marbles (bam). The aim of this project is to determine how BMP signalling regulates GSC identity. To do this the GSC and daughter cell gene expression signatures was uncovered using RNA-seq. In addition, a comparison of genetically expanded GSCs that experience high or low BMP signalling enabled the identification of the BMP-responsive transcriptional network. These data were used to identify GSC-enriched factors and downstream targets of BMP signalling that regulate the formation of microtubule-rich cytoplasmic projections formed by GSCs. Genetic manipulation and live ex vivo imaging reveals that ovarian germ cells also form actinbased projections and both classes of projection permit GSC access to a reservoir of Dpp held away from the GSCs. Moreover, data presented here suggests that microtubule-rich projections, termed 'cytocensors', form downstream of BMP signalling and that these projections represent a specialised signalling compartment, allowing GSCs to dynamically modulate BMP signalling levels through the concentration of BMP receptor and an inhibitor. By enabling the control of BMP receptor activity, it is speculated that these structures enable GSCs to maintain threshold levels of signal activation that permit GSC maintenance whilst allowing timely differentiation upon exiting the niche. Similar cytoskeletal projections could provide a general mechanism allowing stem cells to negotiate complex niche architecture and calibrate signalling response.
Supervisor: Ashe, Mark ; Ashe, Hilary ; Ronshaugen, Matthew Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available