The effects of thyroid hormone on growth factor expression in developing cerebella of mice: In vivo and in vitro studies.
Item
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Title
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The effects of thyroid hormone on growth factor expression in developing cerebella of mice: In vivo and in vitro studies.
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Identifier
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AAI3037390
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identifier
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3037390
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Creator
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Carrasco, Emilce.
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Contributor
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Adviser: Victoria Luine
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Date
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2002
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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In this study, I investigated the effects of thyroid hormone on cerebellar development and growth factor expression, specifically the epidermal growth factor receptor (EGFR), its ligand transforming growth factor-alpha (TGF-alpha), and basic fibroblast growth factor (bFGF) in vivo and in vitro.;In vivo, profiles of thyroid hormone expression were measured in postnatal animals and were found to peak at postnatal day 15 (P15). These levels dropped below detectable levels when mice were made hypothyroid with propylthiouracil (PTU). TGF-alpha and EGFR expression were maximal at P6 in normal animals, but remained low in hypothyroid animals, suggesting that thyroid hormone was responsible for their induction. Immunohistochemical analysis of EGFR protein expression revealed that this receptor was expressed on granule cells within the inner zone of the external granule cell layer (EGL), where post-mitotic granule cells are found. The persistence of EGFR expression on migrating granule cells and subsequent down-regulation of expression in the internal granule cell layer (IGL) implicates a role for EGFR-ligands in migration and/or differentiation. In hypothyroid animals, I observed a delayed progression of granule cell migration, consistent with the persistence of EGFR labeling in the EGL, and in the "pile-up" of labeled cells at the interface between the molecular layer and the IGL.;In vitro, I examined the effects of thyroid hormone on mixed cultures of cerebellar granule neurons and several types of glia, thus permitting biologically relevant neuronal-glial interactions. I found that L-triiodothyronine (T3) had differential effects on neurons and glia, depending on cell density. At low plating densities, T3 accelerated neuronal and glial differentiation and the switch in astrocyte morphology from radial to velate. At high densities, T3 decreased proliferation of non-neuronal cells. Western blotting of cell lysates showed that T3 treatment regulated levels of epidermal growth factor receptor (EGFR), and basic fibroblast growth factor (bFGF) proteins in opposite directions, attenuating bFGF, but inducing EGFR.;Taken together, these results implicate thyroid hormone in the coordinated expression of TGF-alpha and EGFR, which appear to play a role in postmitotic developmental events, and bFGF, which appears to be involved in earlier mitotic events.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
