TY  - GEN
N2  - During 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.
DO  - 10.6083/bpxhc42407
DO  - doi
AB  - During 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.
AD  - Oregon Health and Science University
T1  - New populations of neurons reveal novel mechanisms of cell death and astrocyte-dependent neurite pruning
ED  - Kang, Yunsik
ED  - Freeman, Marc
ED  - Mentor
ED  - PI
DA  - 2023-09-26
AU  - Lehmann, Katherine
L1  - https://digitalcollections.ohsu.edu/record/42407/files/Lehmann.Katherine.2024.pdf
PB  - Oregon Health and Science University
LA  - eng
PY  - 2023-09-26
ID  - 42407
L4  - https://digitalcollections.ohsu.edu/record/42407/files/Lehmann.Katherine.2024.pdf
KW  - Neurosciences
KW  - developmental neuroscience
KW  - neuronal remodeling
TI  - New populations of neurons reveal novel mechanisms of cell death and astrocyte-dependent neurite pruning
Y1  - 2023-09-26
L2  - https://digitalcollections.ohsu.edu/record/42407/files/Lehmann.Katherine.2024.pdf
LK  - https://digitalcollections.ohsu.edu/record/42407/files/Lehmann.Katherine.2024.pdf
UR  - https://digitalcollections.ohsu.edu/record/42407/files/Lehmann.Katherine.2024.pdf
ER  -