Thyroid hormone-responsive genes in developing cerebellum include a novel synaptotagmin and a hairless homolog.
Proper development of the mammalian CNS requires sufficient thyroid hormone; thyroid hormone deficiency during a brief perinatal period produces severe neurological defects in humans and experimental animals. Thyroid hormone exerts its effects through nuclear receptors, which modulate the transcription of downstream genes in response to hormone binding. Surprisingly, few genes that are regulated by thyroid hormone receptors in the CNS have been described. Here, I report the isolation and characterization of genes that are expressed in response to thyroid hormone in developing rat brain. One such gene (Srg1) encodes a novel protein related to synaptotagmin, a protein involved in regulating neurotransmitter release; another (hr) encodes a putative zinc finger protein related to the product of a recently identified mouse gene, hairless. Both Srg1 and hr are induced rapidly (<4 hr), suggesting that they are regulated directly by thyroid hormone. The temporal and spatial expression of both Srg1 and hr is characteristic of genes important to nervous system development. Srg1 and hr are likely part of a cascade of gene activation induced by thyroid hormone that is critical for CNS organization and development.
Thompson
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Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21210, USA.
D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D002135:Calcium-Binding Proteins; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D005796:Genes / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017385:Sequence Homology; D050857:Synaptotagmins; D013963:Thyroid Hormones / Q000494:pharmacology* / Q000502:physiology; D014018:Tissue Distribution; D015533:Transcriptional Activation
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D013963:Thyroid Hormones; D050857:Synaptotagmins