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Pbx, Retina, Gdf6a, Microphthalmia, Topographic mapping

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.





Autor: French, Curtis Robert

Fuente: https://era.library.ualberta.ca/


Introducción



University of Alberta Patterning the zebrafish visual system requires the actions of Pbx transcription factors, and a downstream growth factor, Gdf6a by Curtis Robert French A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Molecular Biology and Genetics Department of Biological Sciences ©Curtis Robert French Fall 2010 Edmonton, Alberta 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 these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the authors prior written permission. Examining Committee Dr.
Andrew Waskiewicz, Department of Biological Sciences, University of Alberta (supervisor) Dr.
Ted Allison, Department of Biological Sciences, University of Alberta Dr.
Shelagh Campbell, Department of Biological Sciences, University of Alberta Dr.
Ordan Lehmann, Department of Ophthalmology, University of Aberta Dr.
James Fadool, Department of Biological Sciences, Florida State University 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 mo...





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