Abstract
Thyroid hormones act directly on gene transcription in the post-natal developing cerebellum, controlling neuronal, and glial cell differentiation. We have combined three experimental approaches to identify the target genes that are underlying this phenomenon: 1) a microarray analysis of gene expression to identify hormone responsive genes in the cerebellum of Pax8-/- mice, a transgenic mouse model of congenital hypothyroidism; 2) a similar microarray analysis on primary culture of cerebellum neurons; and 3) a bioinformatics screen of conserved putative-binding sites in the mouse genome. This identifies surprisingly a small set of target genes, which, for some of them, might be key regulators of cerebellum development and neuronal differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / physiology*
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Animals
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Animals, Newborn
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Cerebellum / growth & development
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Cerebellum / physiology*
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Gene Expression Regulation, Developmental*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Neurons / physiology*
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Oligonucleotide Array Sequence Analysis
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PAX8 Transcription Factor
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Paired Box Transcription Factors / deficiency
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Paired Box Transcription Factors / genetics
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RNA / genetics
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RNA / isolation & purification
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Receptors, Thyroid Hormone / genetics*
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Reverse Transcriptase Polymerase Chain Reaction
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Thyroxine / genetics*
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Triiodothyronine / genetics*
Substances
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PAX8 Transcription Factor
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Paired Box Transcription Factors
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Pax8 protein, mouse
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Receptors, Thyroid Hormone
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Triiodothyronine
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RNA
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Thyroxine