ETD RECORD
The functional roles of retinal homeobox genes in zebrafish retinal development and an introduction to silica nanomaterial toxicity in zebrafish embryos
Citation
Nelson, Steve M.. (2008). The functional roles of retinal homeobox genes in zebrafish retinal development and an introduction to silica nanomaterial toxicity in zebrafish embryos. Theses and Dissertations Collection, University of Idaho Library Digital Collections. https://www.lib.uidaho.edu/digital/etd/items/etd_144.html
- Title:
- The functional roles of retinal homeobox genes in zebrafish retinal development and an introduction to silica nanomaterial toxicity in zebrafish embryos
- Author:
- Nelson, Steve M.
- Date:
- 2008
- Keywords:
- Zebra danio--Genetic aspects Zebra danio--Cytogenetics Zebra danio--Embryos--Genetic aspects Nanostructured materials--Toxicology Nanostructured materials--Toxicity testing Retinal degeneration--Genetic aspects Retina--Diseases
- Program:
- Neuroscience
- Abstract:
- Hereditary retinal degenerations occur with an incidence of approximately one in 3,500 births in the United States. At the cellular level, these disorders are usually characterized by the sequential loss of rod and cone photoreceptors. Many of the genes that have been implicated in retinal degenerations encode proteins that regulate photoreceptor differentiation or are a part of the phototransduction pathway. The human retinal homeobox gene, QRX, is expressed in photoreceptors and quite recently, a defect in this gene has been proposed to lead to the development of retinitis pigmentosa. In the present research, we have identified the developmental sequence of gene expression that gives rise to the rod lineage of photoreceptors and we have placed the zebrafish retinal homeobox 1 (rx1) gene within this lineage. In addition, we have shown that rx1 is expressed in all subclasses of rod and cone photoreceptors. Further studies presented here indicate that rx1 but not rx2 plays a significant role in the proliferation of retinal progenitors early in retinal development and both are required for photoreceptor differentiation later in retinal development. Our findings show that rx genes are necessary for maintaining retinal progenitors in early retinogenesis and are necessary for photoreceptor differentiation.;Nanomaterials have recently emerged as a viable option for the targeted delivery of therapeutic molecules. However, the toxic effects of many nanomaterials remain untested and little is known of their effects on developing embryos. We have tested several silica derived nanomaterials for toxicity in zebrafish embryos and we have shown that silica nanowires are more toxic and cause teratogenic defects when compared to silica nanoparticles. Our study indicates that the predicted LD50 for silica nanowires is very low (1.5 ng/g of tissue). Of perhaps more significance was the observation that silica nanowires were found to cause defects in neurulation leading to death or holoprosencephaly at frequencies well above that described for humans (including stillborns). Our results suggest that further testing of silica nanomaterials will be needed before they can be used as targeted drug delivery platforms.
- Description:
- Thesis (Ph. D., Neuroscience)--University of Idaho, October 2008.
- Major Professor:
- Deborah L. Stenkamp.
- Defense Date:
- October 2008.
- Type:
- Text
- Format Original:
- xv, 172 leaves :col. ill. ;29 cm.
- Format:
- record
Rights
- Rights:
- In Copyright - Educational Use Permitted. For more information, please contact University of Idaho Library Special Collections and Archives Department at libspec@uidaho.edu.
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