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Dissertation
Astrocyte regulation of neuron structure and function mediated by Sonic hedgehog signaling
Doctor of Philosophy (Ph.D.), Drexel University
Mar 2021
DOI:
https://doi.org/10.17918/00000564
Abstract
Astrocytes are important mediators of brain function and are required for diverse processes such as synapse formation, regulation of the ionic environment, and response to injury. Emerging evidence suggests astrocytes are diverse and demonstrate different functions based on the surrounding environment. In the cortex, a subset of astrocytes participates in neuron-astrocyte communication via Sonic hedgehog (Shh) signaling, where a subset of neurons in Layer 5 express and release the ligand Sonic hedgehog and a subset of astrocytes express the Shh-dependent transcription factor, Gli1. In this dissertation, I probe the importance of this neuron-astrocyte communication to determine unique astrocyte-mediated functions in this distinct subpopulation. In Chapter 1, I consider the implications of astrocytic Shh signaling by discussing past research into its role in astrocyte function and highlight a few open questions to consider in the future. In Chapter 2, I utilized a knockout of astrocytic Shh signaling (Gfap Smo CKO) to identify its unique role in synapse organization, plasticity, and function on nearby L5 neurons and astrocyte-mediated K⁺ regulation via expression of Kir4.1. In Chapter 3, I analyzed gene expression in Gli1 astrocytes to determine the molecular implications of neuron-astrocyte Shh signaling and uncovered a unique enrichment of extracellular matrix genes in this subpopulation of astrocytes and a potential role in modulating perineuronal nets surrounding interneurons. Finally, in Chapter 4, I consider the implications of my work and propose future directions and a model for neuron-astrocyte Shh signaling in the brain. The results presented in this dissertation greatly expand our knowledge of astrocyte diversity by identifying novel astrocyte-mediated functions in a distinct molecularly defined subpopulation of astrocytes and provide new insight into neuron-astrocyte communication.
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Details
- Title
- Astrocyte regulation of neuron structure and function mediated by Sonic hedgehog signaling
- Creators
- Steven A. Hill
- Contributors
- Anna Denise R. Garcia (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xi, 135 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 991014961549304721