Cellular and Molecular Analysis of Axon Development in Zebrafish

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Publication Type dissertation
School or College School of Medicine
Department Neurology
Author Xing, Lingyan
Title Cellular and Molecular Analysis of Axon Development in Zebrafish
Date 2015-12
Description Brain wiring is critical for normal brain function, and brain connection defects have been described in many neurodevelopmental disorders. Accurate central nervous system connectivity relies on precise axon navigation. The cellular and molecular mechanisms governing axon guidance during development are important but not well understood. In this dissertation, I utilize zebrafish, a powerful vertebrate model in developmental and genetic studies, to determine the molecular mechanisms regulating axon guidance in vivo. We specifically determine the role of the two molecules FoxP2 and serotonin (5-HT) in axon guidance. We demonstrate that FoxP2, a forkhead-domain transcription factor, is not required for axon guidance, but it reduces the expression levels of a synaptic protein Cntnap2. We also establish that 5-HT and its receptor Htr2a are important for axon guidance. The regulation of 5-HT on axon guidance is mediated by the tyrosine kinase Ephrinb2a. Moreover, we discover that axon guidance defects induced by environmental hypoxia can be rescued by serotonin reuptake inhibitor fluoxetine. I have also developed and implemented a PCR-based high resolution melting analysis (HRMA) for large-scale genotype screening and characterization of genes involved in axon development. Taken together, this work identifies a novel mechanism involved in central nervous system connectivity, and indicates raphe 5-HT neurons act as a sensor to alterations in the developmental environment.
Type Text
Publisher University of Utah
Subject MESH Zebrafish; Axons; Neurotransmitter Agents; Neurodevelopmental Disorders; Forkhead Transcription Factors; Neuronal Plasticity; Serotonergic Neurons; Neurogenesis; Cell Culture Techniques; Chromatin Immunoprecipitation; Gene Regulatory Networks; Kinesin; Ligands; Telencephalon; Diencephalon; Prosencephalon; Central Nervous System; Neural Pathways; Signal Transduction; Receptors, Eph Family; Membrane Proteins; Physiological Processes
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital version of Cellular and Molecular Analysis of Axon Development in Zebrafish
Rights Management Copyright © Lingyan Xing 2015
Format Medium application/pdf
Format Extent 2,055,620 bytes
Source Original in Marriott Library Special Collections
ARK ark:/87278/s6d255wj
Setname ir_etd
Date Created 2016-04-08
Date Modified 2021-05-06
ID 197340
Reference URL https://collections.lib.utah.edu/ark:/87278/s6d255wj
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