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Transcription factor coexpression with GABAergic and glycinergic terminal differentiation genes
Teasley, Daniel Cole
Teasley, Daniel Cole
Abstract
The adoption of neurotransmitter phenotype is a crucial step in the development of the nervous system. Ca2+ transients have been shown to play a critical role by modulating neurotransmitter phenotype specification during differentiation. The mechanisms by which this occurs remain unclear, but given that Ca2+ affects terminal differentiation gene expression, transcription factors may be regulated by the Ca2+ transients. As a first necessary step in elucidating the effects of Ca2+ on transcription factors in neuronal development, we have characterized the coexpression patterns of transcription factors with terminal differentiation genes to provide a baseline for future studies. We have found that the transcription factors xDlx2 and xDlx5 colocalize extensively with both xGAD67 and xVIAAT in the telencephalon and diencephalon in very similar patterns. xPitx2 is coexpressed moderately with both xGAD67 and xGAT1 in the midbrain, and xPtf1a colocalizes moderately with xGAD67 in the retina. Xbh1 colocalizes extensively with xGlyT1 in the retina. Interestingly, xPitx2 is expressed mutually exclusive to xGAD67 and xGAT1 in the diencephalon with virtually no colocalization. Similarly, Xbh1 is expressed in a mutually exclusive pattern to xGAD67 and xVIAAT in the midbrain. All of these observations lead to several conclusions, among them that the similar coexpression patterns observed for xGAD67, xGAT1, and xVIAAT with several transcription factors suggest that the GABAergic terminal differentiation genes are all subject to similar transcriptional regulatory mechanisms. Furthermore, the mutually exclusive expression patterns observed suggest that either negative regulatory mechanisms or signaling mechanisms play a role in the specification of GABAergic terminal differentiation genes in certain regions of the central nervous system. Finally, overlap observed in transcription factor expression patterns, a transcription factor binding site analysis, and the variability of transcription factor expression along the anterior-posterior axis suggest that inhibitory neurotransmitter phenotype specification is controlled by multiple transcription factors in a combinatorial fashion.
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Thesis is part of Honors ETD pilot project, 2008-2013. Migrated from Dspace in 2016.
Date
2008-05-16
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Keywords
GABA, Development, Nervous system, Differentiation
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Department
Biology