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Title: Programmed cell death generates neural network diversity in flies
Author: Pop, Sinziana
ISNI:       0000 0004 8505 3346
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
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During larval life in Drosophila melanogaster, the adult thoracic ventral nerve cord develops from repeated modules of 26 neural lineages. In 18-21 lineages (depending on thoracic segment), programmed cell death is responsible for eliminating as many as half of newly-born neurons (in one hemilineage) in a stereotyped manner. I set out to investigate the role of programmed cell death in the development of the thoracic nervous system of dipterans with two main questions in mind: 1) If cell death is blocked, can rescued cells become mature neurons and integrate in the underlying neural network? 2) Is hemilineage-specific programmed cell death responsible for sculpting the thoracic neural networks of dipterans which have evolved adaptations to novel habitats? I confirm that hemilineage-specific cell death takes place early in postembryonic neurogenesis in the ventral nerve cord of fruit flies, killing newly-born undifferentiated neurons. When I block death in one specific 'doomed' hemilineage in Drosophila, the resulting 'zombie' cells assume a neuronal identity, survive into adulthood, elaborate branches within the neuropil, extend primary neurites through thoracic nerves and, when activated using thermogenetic tools, elicit behaviour in the adult fly. To establish if hemilineages are homologous in dipterans, I identify and compare thoracic hemilineages in two species of flightless dipterans, the swift louse and the bee louse. In bee lice, but not in swift lice, I observe clear reductions in fiber tract diameter in several hemilineages which have been found to innervate the flight neuropil and/or induce flight-associated behaviours in fruit flies. Consistent with the evolution of flightlessness in swift lice I observe a loss of segment specificity in octopaminergic neuron numbers. I characterise the pattern of cell death in developing swift lice using antibodies for the effector caspase cleaved Dcp-1 and I identify two stages, an early cell death of newly-born cells which takes place in lineages with doomed hemilineages and a later neuronal death that eliminates neurons in surviving hemilineages. When comparing the pattern of early cell death in swift lice and fruit flies I discover dying cells in several flight lineages in swift lice, but not in fruit flies. Taken together, these findings suggest that: 1) Manipulating hemilineage-specific cell death has the potential to generate novel functional networks. 2) The extent and pattern of cell death in hemilineages may have been adjusted during evolution to change network components in flightless dipterans.
Supervisor: Williams, Darren ; Wingate, Richard James Tobias Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available