000042407 001__ 42407
000042407 005__ 20240124114342.0
000042407 0247_ $$2doi$$a10.6083/bpxhc42407
000042407 037__ $$aETD
000042407 041__ $$aeng
000042407 245__ $$aNew populations of neurons reveal novel mechanisms of cell death and astrocyte-dependent neurite pruning
000042407 260__ $$bOregon Health and Science University
000042407 269__ $$a2023-09-26
000042407 336__ $$aDissertation
000042407 502__ $$bPh.D.
000042407 502__ $$gNeuroscience
000042407 520__ $$aDuring animal development, nervous systems over-wire and then refine to shape precise neuronal circuitry. This developmental neuronal remodeling, observed across evolution, involves the selective pruning of synapses, neurites or whole neurons, to refine circuit connectivity, however the molecular mechanisms that drive this process have proven to be complex and diverse. To untangle this complexity, I performed a large-scale screen in Drosophila to discover new mechanisms of developmental neuronal remodeling. Here I describe two newly-identified populations of Drosophila neurons, tracked temporally at single-cell resolution, that remodel in a novel manner. The neurons—which we refer to as the Beat-Va lateral (Beat-VaL) and Beat-Va medial (Beat-VaM) populations—undergo cell local pruning and cell death, respectively. Beat-VaL cells use hormone signaling, caspase activation and Hox genes to execute cell death. This is the first time that both hormone signaling and Hox genes have been shown to be necessary for neuronal cell death in the same population of neurons. In the Beat-VaM population, astrocytes are necessary for the fragmentation step of remodeling. This is the first-time astrocytes specifically have been implicated in a non-redundant fashion in neuronal fragmentation in the fly. These findings demonstrate 1) a new mechanism for cell death that relies on intersectional Hox gene and hormone receptor expression 2) a novel mechanism for neurite pruning involving astrocytes and 3) that astrocytes play unique and crucial roles at specific stages during the remodeling process. Furthermore, I present preliminary data on three other populations of neurons that remodel during metamorphosis, and which could be informative in future studies.
000042407 536__ $$oNational Science Foundation $$cDGE-1448072
000042407 540__ $$fCC BY
000042407 542__ $$fIn copyright - single owner
000042407 650__ $$aNeurosciences$$022870
000042407 651__ $$aOregon$$041094
000042407 6531_ $$adevelopmental neuroscience
000042407 6531_ $$aneuronal remodeling
000042407 691__ $$aSchool of Medicine$$041369
000042407 692__ $$aVollum Institute$$041509
000042407 7001_ $$aLehmann, Katherine$$uOregon Health and Science University$$041354$$10000-0002-0323-879X
000042407 7201_ $$aKang, Yunsik$$uOregon Health and Science University$$041354$$eMentor$$7Personal
000042407 7201_ $$aFreeman, Marc$$uOregon Health and Science University$$041354$$ePI$$7Personal
000042407 789__ $$eHas part$$whttps://doi.org/10.1101/2023.12.05.570324$$2DOI
000042407 792__ $$aAstrocyte-dependent local neurite pruning and Hox gene-mediated cell death in Beat-Va neurons
Katherine S Lehmann, Madison T Hupp, Amanda Jefferson, Ya-Chen Cheng, Amy E Sheehan, Yunsik Kang, Marc R Freeman
000042407 8564_ $$94847f9bf-61f5-4c7d-b5b2-d28b1e717600$$s12604905$$uhttps://digitalcollections.ohsu.edu/record/42407/files/Lehmann.Katherine.2024.pdf
000042407 909CO $$ooai:digitalcollections.ohsu.edu:42407$$pstudent-work
000042407 980__ $$aTheses and Dissertations
000042407 981__ $$aPublished$$b2024-01-11