Development, Disease, and Regeneration: Using Zebrafish to Model Neurological PerturbationsThorn, Robert JosephcreatorHart, AnneReaderWessel, GaryReaderCreton, RobbertAdvisorMowry, KimberlyReaderDeLong, AlisonReaderAluru, NeelReaderBrown University. Department of Molecular Biology, Cell Biology and Biochemistrysponsor2018xiv, 170 p.born digitalThesis (Ph. D.)--Brown University, 2018thesesAs medical technologies advance, effective vertebrate models of human disease are vital to determine safety and efficacy of treatments. My research has further developed zebrafish as a model to investigate vertebrate neurological development and disease. Zebrafish are well suited for use as a model of vertebrate disease. A mixed population of male and female fish can produce hundreds of embryos on a daily basis. The embryos are transparent, develop externally, and can be imaged live by light microscopy throughout development. They are accessible to genetic manipulation and have many genes that are homologous to human disease genes. Zebrafish larvae display robust stereotyped behaviors that can be assayed to detect subtle brain defects. In my thesis work, I used zebrafish to model developmental sensitivities to immunosuppressant drugs that may be prescribed during human fetal development. My research indicated that these drugs have a negative effect on brain and behavioral development. I’ve shown that zebrafish are also useful in testing neurodevelopmental toxicity of small molecules. Additionally, I have used morpholinos in zebrafish to knock down calcineurin, whose decreased signaling has been implicated in Down syndrome disease phenotypes. My research displayed developmental brain defects and behavioral defects in the calcineurin morphants, potentially due to increased apoptosis early in development. This model can also be utilized to test pharmaceuticals that may treat Down syndrome phenotypes. Finally, I used zebrafish as a high-throughput model for the loss and recovery of vertebrate vision. My work showed that zebrafish behavior can be used as a method to detect loss and recovery of larval zebrafish vision in multi-well plates. This model will be useful in testing compounds to treat human visual diseases, especially those that may be used in conjunction with promising stem cell therapies. Overall my research has made strides in using zebrafish as a vertebrate model of neurodevelopmental aberrations and potential therapeutic screening of pharmaceutical compounds.ZebrafishBrain DevelopmentBrain--DiseasesZebrafish BehaviorEnglishRPB2018061810.26300/aeew-em57In CopyrightCollection is open for research.dissertations