Spelling suggestions: "subject:"retinal development""
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Protocadherin-17 Function in Zebrafish Retina DevelopmentChen, Yun 11 December 2012 (has links)
No description available.
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Identification of echinus and characterization of its role in Drosophila eye developmentBosdet, Ian Edward 11 1900 (has links)
The precise structure of the adult Drosophila eye results from a coordinated process of cell sorting, differentiation and selective cell death in the retinal epithelium. Mutations in the gene echinus cause supernumerary pigment cells due to insufficient cell death. This study reports the identification of echinus and the characterization of its role in Drosophila retinal development. Using a combination of deletion mapping, gene expression analysis and genomic sequencing, echinus was cloned and several alleles were sequenced. echinus encodes a ~180kDa protein containing an ubiquitin hydrolase domain at its N-terminus and a polyglutamine tract at its C-terminus. echinus is expressed in the retina during pupal development and mutants of echinus have decreased levels of apoptosis during several stages of retinal development. Defects in the cell sorting process that precedes cell death are also observed in echinus loss-of-function mutants and echinus overexpression can cause defects in ommatidial rotation and the morphology of cone cells. echinus is a positive regulator of DE-cadherin and Enabled accumulation in adherens junctions of retinal epithelial cells. Genetic interactions were observed between echinus and the genes wingless, enabled and expanded. An immunofluorescence assay in Drosophila S2 cell cultured demonstrated that Echinus localizes to intracellular vesicles that do not appear to be endocytic in nature, and the C-terminal region of Echinus was shown to be necessary for this association. A protein interaction screen using an immunoprecipitation and mass spectrometry approach identified interactions between Echinus and the vesicle coat protein Clathrin, the scaffolding protein RACK1 and the casein kinase I epsilon (Dco). Co-immunoprecipitation additionally identified an interaction between Echinus and Enabled. This work has revealed echinus to be an important regulator of cell sorting and adherens junction formation in the developing retina and has identified multiple interactions between echinus and enabled, a regulator of the actin cytoskeleton.
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Identification of echinus and characterization of its role in Drosophila eye developmentBosdet, Ian Edward 11 1900 (has links)
The precise structure of the adult Drosophila eye results from a coordinated process of cell sorting, differentiation and selective cell death in the retinal epithelium. Mutations in the gene echinus cause supernumerary pigment cells due to insufficient cell death. This study reports the identification of echinus and the characterization of its role in Drosophila retinal development. Using a combination of deletion mapping, gene expression analysis and genomic sequencing, echinus was cloned and several alleles were sequenced. echinus encodes a ~180kDa protein containing an ubiquitin hydrolase domain at its N-terminus and a polyglutamine tract at its C-terminus. echinus is expressed in the retina during pupal development and mutants of echinus have decreased levels of apoptosis during several stages of retinal development. Defects in the cell sorting process that precedes cell death are also observed in echinus loss-of-function mutants and echinus overexpression can cause defects in ommatidial rotation and the morphology of cone cells. echinus is a positive regulator of DE-cadherin and Enabled accumulation in adherens junctions of retinal epithelial cells. Genetic interactions were observed between echinus and the genes wingless, enabled and expanded. An immunofluorescence assay in Drosophila S2 cell cultured demonstrated that Echinus localizes to intracellular vesicles that do not appear to be endocytic in nature, and the C-terminal region of Echinus was shown to be necessary for this association. A protein interaction screen using an immunoprecipitation and mass spectrometry approach identified interactions between Echinus and the vesicle coat protein Clathrin, the scaffolding protein RACK1 and the casein kinase I epsilon (Dco). Co-immunoprecipitation additionally identified an interaction between Echinus and Enabled. This work has revealed echinus to be an important regulator of cell sorting and adherens junction formation in the developing retina and has identified multiple interactions between echinus and enabled, a regulator of the actin cytoskeleton.
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Identification of echinus and characterization of its role in Drosophila eye developmentBosdet, Ian Edward 11 1900 (has links)
The precise structure of the adult Drosophila eye results from a coordinated process of cell sorting, differentiation and selective cell death in the retinal epithelium. Mutations in the gene echinus cause supernumerary pigment cells due to insufficient cell death. This study reports the identification of echinus and the characterization of its role in Drosophila retinal development. Using a combination of deletion mapping, gene expression analysis and genomic sequencing, echinus was cloned and several alleles were sequenced. echinus encodes a ~180kDa protein containing an ubiquitin hydrolase domain at its N-terminus and a polyglutamine tract at its C-terminus. echinus is expressed in the retina during pupal development and mutants of echinus have decreased levels of apoptosis during several stages of retinal development. Defects in the cell sorting process that precedes cell death are also observed in echinus loss-of-function mutants and echinus overexpression can cause defects in ommatidial rotation and the morphology of cone cells. echinus is a positive regulator of DE-cadherin and Enabled accumulation in adherens junctions of retinal epithelial cells. Genetic interactions were observed between echinus and the genes wingless, enabled and expanded. An immunofluorescence assay in Drosophila S2 cell cultured demonstrated that Echinus localizes to intracellular vesicles that do not appear to be endocytic in nature, and the C-terminal region of Echinus was shown to be necessary for this association. A protein interaction screen using an immunoprecipitation and mass spectrometry approach identified interactions between Echinus and the vesicle coat protein Clathrin, the scaffolding protein RACK1 and the casein kinase I epsilon (Dco). Co-immunoprecipitation additionally identified an interaction between Echinus and Enabled. This work has revealed echinus to be an important regulator of cell sorting and adherens junction formation in the developing retina and has identified multiple interactions between echinus and enabled, a regulator of the actin cytoskeleton. / Medicine, Faculty of / Medical Genetics, Department of / Graduate
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Expression of the Cyclin-Dependent Kinase Inhibitor p27Kip1 by Developing Retinal Pigment EpitheliumDefoe, Dennis M., Levine, Edward M. 01 October 2003 (has links)
The cyclin-dependent kinase (Cdk) inhibitor p27Kip1 contributes to the timing of cell cycle withdrawal during development and, consequently, in organogenesis. Within the retina, this effector protein is up-regulated during the birth of neuronal and glial cells [Dev. Biol. (2000) 299]. However, its expression within the retinal pigment epithelium (RPE), a supporting cell layer that is essential for neural retina development and function, has not previously been reported. We show that p27Kip1 protein expression in the RPE occurs in two phases: an up-regulation during mid-to late embryonic stages and a down-regulation during the subsequent postnatal period. In the early phase of up-regulation, an inverse relationship is seen between expression of p27Kip1 and PCNA, an indicator of cycling cells. During both up-and down-regulation, the change in spatial pattern of expression proceeds in a central to peripheral manner, with p27Kip1 up-regulation paralleling retinal maturation. These data suggest that this cell cycle regulator may be an important factor controlling the timing of RPE cell cycle withdrawal.
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Requirements for ARS2 in RNA processing and retina developmentO'Sullivan, Connor 02 September 2016 (has links)
ARS2 is a stable component of the nuclear cap-binding complex (CBC) and is critical for RNA Polymerase II transcript processing. As such, ARS2 functions in numerous RNA Polymerase II transcript processing events, which happen co-transcriptionally from initiation to termination, and post-transcriptionally during maturation and export into the cytoplasm. Developmentally, ARS2 is essential for stem cell maintenance and differentiation during embryogenesis and in neural stem cells. Two major questions in the field were: 1) how does ARS2 function in stem cell maintenance and/or differentiation? and 2) how does ARS2 distinguish between disparate RNA classes and processing complexes? In chapter 2, I show that ARS2 is required for the proliferation and cell fate decisions of progenitors in the mouse retina. Specifically, ARS2 knockdown delays cell cycle progression and leads to premature cell cycle exit. Additionally, ARS2 knockdown increases the proportion of cells expressing rod photoreceptor marker Nrl, and decreases Müller glial marker expression. Similarly, knockdown of FLASH, an essential component for replication-dependent histone transcript processing and cell cycle progression, increases the proportion of cells expressing the Nrl reporter, suggesting ARS2’s role in histone processing is contributing to cell cycle progression and fate specification in the developing retina. In chapter 3, I used bioinformatics analysis and homology modeling to classify four structural domains of mammalian ARS2, including a newly identified RNA recognition motif (RRM), and performed mutagenesis to assess their functions. The unstructured C-terminus is required for interaction with the CBC, the Mid domain is implicated in binding DROSHA, which is required for microRNA biogenesis, while the zinc finger and RRM are involved in binding FLASH. Moreover, the zinc finger is required for interacting with RNA. Collectively, this work establishes a model where ARS2 acts as a scaffold, using multiple domains to interact with distinct processing complexes in a mutually exclusive manner. It is also the first study describing the requirements of ARS2 in the developing retina. Understanding the molecular mechanisms governing progenitor proliferation and cell fate specification is crucial in order to design therapies for retinal degenerative diseases. / Graduate / 0487
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