Mechanisms of cell death in the developing mouse limb.
Item
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Title
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Mechanisms of cell death in the developing mouse limb.
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Identifier
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AAI9707063
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identifier
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9707063
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Creator
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Ahuja, Harleen Singh.
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Contributor
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Adviser: Zahra Zakeri
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Date
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1996
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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, Molecular | Biology, Cell
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Abstract
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Cell death is an important biological process that selectively eliminates cells in embryonic and adult tissues. The mechanisms underlying this selective elimination are unknown. The aim of this work has been to use several approaches to study cell death in the developing mouse limb. We have both examined the expression of cell death implicated genes and established the nature of cell death during limb development. Using a line of mutant mice which displays a limb deformity, we show that this defect is the result of a deformity in the pattern of cell death. To address the regulation of cell death, we performed a comparative study of normal and mutant limbs by analyzing the expression profile of genes associated with cell death, limb patterning, and cell cycle. These genes have been directly or indirectly implicated in cell death. We show that clusterin is not universally associated with cell death. We did not find any alteration in the pattern of expression of bcl-2 (b cell lymphoma) or Msx (muscle segment) genes in normal versus mutant limbs. Tissue transglutaminase and cyclin dependent kinase 5 (Cdk5) were associated specifically with dying cells of the developing limb. Finally, we have shown that we can selectively increase cell death in the limb by exposure of embryos to retinoic acid (RA). We illustrate that the nature of RA cell killing is similar to normal cell death and that the genetically altered pattern of cell death in the Hm limb can be overcome by treatment of the embryo with RA at day 14 of gestation. To determine the mechanism of this selective cell killing by RA, we examined the expression of the retinoic acid receptor {dollar}\beta{dollar} and a transgene containing a retinoic acid response element. The regulation of RA action seems to be independent of receptor expression and endogenous RA availability. We conclude that cell death is an important aspect of limb development and that it is dependent on a variety of signaling molecules that initiate the process, such as RA, and a number of factors such as Cdk5 and tissue transglutaminase that mediate it.
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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.
