Dorsal-Ventral Retinal Patterning: Genetic Mechanisms for the Development of a Topographic Map

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Publication Type dissertation
School or College School of Medicine
Department Neurology
Author Kruse-Bend, Renee Claire
Title Dorsal-Ventral Retinal Patterning: Genetic Mechanisms for the Development of a Topographic Map
Date 2012-08
Description Topographic connections of retinal axons with their brain targets allow us to perceive a spatially organized image of the visual world. Achieving this precise retinotopic axon targeting during development first requires the patterning of origin (retina) and target (brain) tissues along anterior-posterior (A-P) and dorsal-ventral (D-V) axes, such that individual cells of both tissues acquire a molecularly specified positional identity. The research presented in my dissertation addresses the processes involved in patterning the dorsal-ventral axis of the retina and forming dorsal-ventral retinotopic projections. First, I studied what tissues and signals are involved in the initiation of dorsal polarity. I found that the dorsolateral region of the optic vesicle is the first domain to upregulate dorsal-specific transcription factors. My expression studies, combined with my fate map experiments, suggested that these dorsolateral optic vesicle cells continue expressing dorsal markers throughout optic vesicle morphogenesis, and eventually contribute to dorsal and central retina. I also showed that the BMP family gene gdf6a is necessary for initiation of dorsal retinal fate. Importantly, I found that gdf6a acts early during optic vesicle evagination (10-12 hpf) when it is expressed in the extraocular head ectoderm overlying the region of dorsolateral optic vesicle that first expresses dorsal-specific transcription factors. Finally, I showed that the bmp2b gene is also necessary for dorsal retinal fate initiation, acting upstream of gdf6a. Secondly, I performed a forward genetic screen to search for novel genes that specify the dorsal-ventral axis of the retina. By screening for mutants with altered expression of D-V markers, I identified a novel gene, bigtop, required for dorsal-ventral retinal patterning, eye development, and retinotectal projections. This mutation was mapped to a four-megabase region on chromosome two. My studies addressed the following question: how is the retina patterned early during development in order to specify retinal ganglion cells with positional fate? Altogether, my studies advanced the field of D-V retinal patterning by identifying an extraocular dorsal retinal initiation signal, uncovering the role of bmp2b in dorsal retinal initiation, and identifying a novel mutant necessary for D-V patterning.
Type Text
Publisher University of Utah
Subject Neurosciences; Developmental biology
Subject MESH Retinal Ganglion Cells; Zebrafish; Axons; Body Patterning; Embryonic Development; Retina; Ectoderm; Visual Pathways; Zebrafish Proteins; Gene Expression Regulation, Developmental; Growth Differentiation Factor 6; Topographic Mapping
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of Dorsal-Ventral Retinal Patterning: Genetic Mechanisms for the Development of a Topographic Map. Spencer S. Eccles Health Sciences Library. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Renee Claire Kruse-Bend 2012
Format Medium application/pdf
Format Extent 19,301,512 bytes
Source Original in Marriott Library Special Collections, QP6.5 2012.K78
ARK ark:/87278/s6d82kmv
Setname ir_etd
Date Created 2014-04-10
Date Modified 2021-05-06
ID 196310
Reference URL
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