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An investigation of the role of Ikar...
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Ring, Mary Ann.
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An investigation of the role of Ikaros in the differentiation of enkephalinergic neurons in the striatum.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
An investigation of the role of Ikaros in the differentiation of enkephalinergic neurons in the striatum./
Author:
Ring, Mary Ann.
Description:
151 p.
Notes:
Directors: Denes V. Agoston; Sally A. Moody.
Contained By:
Dissertation Abstracts International62-11B.
Subject:
Biology, Genetics. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3032765
ISBN:
0493452680
An investigation of the role of Ikaros in the differentiation of enkephalinergic neurons in the striatum.
Ring, Mary Ann.
An investigation of the role of Ikaros in the differentiation of enkephalinergic neurons in the striatum.
- 151 p.
Directors: Denes V. Agoston; Sally A. Moody.
Thesis (Ph.D.)--The George Washington University, 2002.
Enkephalinergic neurons are most abundant in the basal ganglia where very large numbers of neurons in the caudate-putamen express the enkephalin gene and use the various enkephalin peptides as neurotransmitters. In contrast, neurons of the pallidum and thalamus do not express the enkephalin gene, and the cortex has very few enkephalinergic neurons. To gain a better understanding of the mechanisms regulating the establishment of the enkephalin phenotype during development, studies focused on identifying cis-elements within the enkephalin gene where trans-acting factors bind to control gene transcription. We identified binding sites for the transcription factor Ikaros within the −2.7kb upstream region of the rat enkephalin gene. Given the central regulatory role of Ikaros in the differentiation of lymphoid cells, we investigated the role of Ikaros in the differentiation of enkephalinergic neurons in the striatum.
ISBN: 0493452680Subjects--Topical Terms:
1017730
Biology, Genetics.
An investigation of the role of Ikaros in the differentiation of enkephalinergic neurons in the striatum.
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151 p.
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Directors: Denes V. Agoston; Sally A. Moody.
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Source: Dissertation Abstracts International, Volume: 62-11, Section: B, page: 4921.
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Thesis (Ph.D.)--The George Washington University, 2002.
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Enkephalinergic neurons are most abundant in the basal ganglia where very large numbers of neurons in the caudate-putamen express the enkephalin gene and use the various enkephalin peptides as neurotransmitters. In contrast, neurons of the pallidum and thalamus do not express the enkephalin gene, and the cortex has very few enkephalinergic neurons. To gain a better understanding of the mechanisms regulating the establishment of the enkephalin phenotype during development, studies focused on identifying cis-elements within the enkephalin gene where trans-acting factors bind to control gene transcription. We identified binding sites for the transcription factor Ikaros within the −2.7kb upstream region of the rat enkephalin gene. Given the central regulatory role of Ikaros in the differentiation of lymphoid cells, we investigated the role of Ikaros in the differentiation of enkephalinergic neurons in the striatum.
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Analyses by RT-PCR, Western blotting and immunohistochemistry showed that Ikaros is expressed in the striatum between embryonic day 12 and postnatal day 2, but not in the adult. Ikaros-expressing cells are predominantly postmitotic, differentiating neurons and many also express enkephalin. A series of electrophoretic mobility shift assays confirmed that Ikaros protein binds specifically to a motif in the upstream region of the rat and mouse enkephalin genes. Competitive transient transfection assays in primary striatum cultures suggested that Ikaros is an activator of gene transcription in differentiating striatal neurons. However, analysis of Ikaros null mutant mice by <italic> in situ</italic> hybridization and immunohistochemistry showed no significant effects on the levels of enkephalin mRNA, other striatal genes dynorphin and substance P, or the total number of striatal neurons.
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These experiments demonstrated that Ikaros is expressed in a spatial and temporal pattern consistent with the establishment of the enkephalin phenotype in the striatum and that Ikaros can bind to the enkephalin gene to upregulate its transcription, but the role for Ikaros <italic>in vivo</italic> is uncertain. Overall, these experiments provide a basis for future studies that include the identification and characterization of other proteins that may interact with Ikaros and the functional implications of these interactions on the differentiation of the enkephalinergic phenotype. Such studies will advance our understanding of the transcriptional events regulating neurogenesis, particularly those controlling differentiation into the enkephalin phenotype.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3032765
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