{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"The Role of Dystroglycan in Differentiating Oligodendroglia and CNS Myelination","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/1951/60214"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"During central nervous system (CNS) development, individual oligodendrocytes myelinate multiple axons, thus requiring the outgrowth \nand extensive branching of oligodendroglial processes. Extrinsic cues including the extracellular matrix (ECM) molecule laminin regulate oligodendrocyte \nmaturation; indeed, laminin-deficient mice have fewer myelinated axons, which may indicate a defect in the ability to properly extend and branch processes. \nIt remains unclear, however, to what extent ECM receptors contribute to oligodendroglial process remodeling itself. Here I report that the ECM receptor \ndystroglycan is necessary for laminin enhancement of filopodial formation, process outgrowth, and process branching in differentiating oligodendroglia. \nDuring early oligodendroglial differentiation, the disruption of dystroglycan-laminin interactions, via blocking antibodies or dystroglycan siRNA, resulted \nin decreased filopodial number and length, decreased process length, and decreased numbers of primary and secondary processes. Later in oligodendrocyte \ndifferentiation, dystroglycan-deficient cells developed fewer branches, thus producing less complex networks of processes as determined by Sholl analysis. \nIn newly-differentiating oligodendroglia dystroglycan was localized in filopodial tips, while in more mature oligodendrocytes dystroglycan was enriched in \nFAK-positive focal adhesion structures. In addition to its role in promoting cytoskeletal reorganization, I have recently begun investigating a novel \nsignaling role for dystroglycan in the nucleus. Our preliminary evidence suggests that dystroglycan localizes to the nucleus in oligodendrocyte progenitors \n(OPCs) and may play a role in dystroglycan-dependent modulation of oligodendroglial differentiation. \u00ce -dystroglycan expression in the nuclear fraction of \nproliferating OPCs is higher than in differentiating oligodendrocytes; furthermore, I have detected an increased proportion of a cleaved form of \n\u00ce -dystroglycan in the nucleus of proliferating OPCs relative to differentiated oligodendrocytes. Analysis of OPCs expressing a dystroglycan deletion \nconstruct reveal a preferential localization of the cytoplasmic domain of \u00ce -dystroglycan to the nucleus, and decreased proliferation in response to growth \nfactor stimulation. Our results suggest that dystroglycan may contribute to the overall myelinogenic capacity of individual oligodendroglia by influencing \noligodendroglial process dynamics through dystroglycan-laminin interactions, and potentially modulating differentiation by signaling in the nucleus of \noligodendroglial progenitors."},{"label":"dcterms.available","value":"2013-05-24T16:38:14Z"},{"label":"dcterms.contributor","value":"Colognato, Holly"},{"label":"dcterms.creator","value":"Eyermann, Christopher Edward"},{"label":"dcterms.dateAccepted","value":"2015-04-24T14:45:43Z"},{"label":"dcterms.dateSubmitted","value":"2013-05-24T16:38:14Z"},{"label":"dcterms.description","value":"Department of Molecular and Cellular Pharmacology"},{"label":"dcterms.extent","value":"149 pg."},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/71049"},{"label":"dcterms.issued","value":"2012-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2015-04-24T14:45:43Z (GMT). No. of bitstreams: 3\nStonyBrookUniversityETDPageEmbargo_20130517082608_116839.pdf.jpg: 1934 bytes, checksum: c116f0e1e7be19420106a88253e31f2e (MD5)\nStonyBrookUniversityETDPageEmbargo_20130517082608_116839.pdf.txt: 336 bytes, checksum: 84c0f8f99f2b4ae66b3cc3ade09ad2e9 (MD5)\nStonyBrookUniversityETDPageEmbargo_20130517082608_116839.pdf: 41286 bytes, checksum: 425a156df10bbe213bfdf4d175026e82 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Beta Dystroglycan, Dystroglycan, Nucleus, Oligodendrocyte, Process Branching, Process Outgrowth"},{"label":"dcterms.title","value":"The Role of Dystroglycan in Differentiating Oligodendroglia and CNS Myelination"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/19%2F80%2F65%2F19806563035222613835929733934784407428/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/19%2F80%2F65%2F19806563035222613835929733934784407428","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}