Thyroid Hormone-Responsive Genes in Developing Cerebellum Include a Novel Synaptotagmin and ahairlessHomolog

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Abstract
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. BothSrg1andhrare induced rapidly (Srg1andhris characteristic of genes important to nervous system development.Srg1andhrare likely part of a cascade of gene activation induced by thyroid hormone that is critical for CNS organization and development.