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Permanent link (DOI): https://doi.org/10.7939/R34X6P

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Patterning the zebrafish visual system requires the actions of Pbx transcription factors, and a downstream growth factor, Gdf6a Open Access

Descriptions

Other title
Subject/Keyword
Pbx
Retina
Gdf6a
Microphthalmia
Topographic mapping
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
French, Curtis Robert
Supervisor and department
Dr. Andrew Waskiewicz (Department of Biological Sciences, University of Alberta)
Examining committee member and department
Dr. Ordan Lehmann (Department of Medical Genetics, University of Alberta)
Dr. James Fadool (Department of Biological Sciences, Florida STate University)
Dr. Shelagh Campbell (Department of Biological Sciences, University of Alberta)
Dt. W. Ted Allison (Department of Biological Sciences, University of Alberta)
Department
Department of Biological Sciences
Specialization

Date accepted
2010-09-29T19:28:49Z
Graduation date
2010-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
The zebrafish visual system relies on positional information in the retina and optic tectum, so that the spatial fidelity of light signals that enter the eye are preserved for visual processing. This positional information is essential for ordered topographic mapping of retinal ganglion cell axons. Spatial information in the retina and tectum relies on discrete signaling pathways that regulate polarized expression of axon guidance molecules in distinct domains in both the retina and tectum, thereby ensuring that accurate topographic maps are created. In this thesis, I have investigated the function of two families of transcription factors, Pbx and Meis, as well as a growth factor of the Bmp family, Gdf6a, in specifying positional identity in the zebrafish visual system. I demonstrate that two partially redundant pbx genes, pbx2 and pbx4, along with members of the meis family, are required for patterning of the dorsal retina and tectum in zebrafish. Embryos lacking these critical transcription factors exhibit retinal ganglion cell axon outgrowth errors, which are likely the result of tectal mis-patterning. Bone morphogenetic protein (Bmp) growth factors regulate dorsal retinal identity in vertebrate models, but the developmental timing of this signaling remains unclear. In this thesis, I investigate the functions of two zebrafish Bmps, Gdf6a and Bmp4, during initiation of dorsal retinal identity. Knockdown of zebrafish Gdf6a blocks initiation of dorsal marker expression, while knockdown of Bmp4 produces no discernable retinal phenotype. These data, combined with analyses of embryos ectopically expressing Bmps, demonstrate that Gdf6a is necessary and sufficient for initiation of dorsal retinal identity, and loss of such identity leads to errors in retinal ganglion cell topographic mapping. Finally, I demonstrate that gdf6a is required for numerous embryonic processes in addition to dorsal retina specification. Gdf6a in required for eye growth, as loss of Gdf6a function leads to microphthalmia. I have obtained preliminary evidence that this growth factor is also required for development of the lens and axial skeleton. Furthermore, many of these phenotypes are similar to those seen in human patients with mutations in GDF6, highlighting the importance of understanding the function of this growth factor in model organisms.
Language
English
DOI
doi:10.7939/R34X6P
Rights
License granted by Curtis French (crfrench@ualberta.ca) on 2010-09-27T19:54:44Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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