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Volume 272, Number 13, Issue of March 28, 1997 pp. 8179-8188
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development

(Received for publication, September 19, 1996, and in revised form, November 21, 1996)

Robert J. Denver , Sushama Pavgi and Yun-Bo Shi ^¶

From the  Department of Biology, The University of Michigan, Ann Arbor, Michigan 48109 and the ^¶ Laboratory of Molecular Embryology, NICHD, National Institutes of Health, Bethesda, Maryland 20892

Although thyroid hormone (TH) plays a significant role in vertebrate neural development, the molecular basis of TH action on the brain is poorly understood. Using polymerase chain reaction-based subtractive hybridization we isolated 34 cDNAs for TH-regulated genes in the diencephalon of Xenopus tadpoles. Northern blots verified that the mRNAs are regulated by TH and are expressed during metamorphosis. Kinetic analyses showed that most of the genes are up-regulated by TH within 4-8 h and 13 are regulated by TH only in the brain. All cDNA fragments were sequenced and the identities of seven were determined through homology with known genes; an additional five TH-regulated genes were identified by hybridization with known cDNA clones. These include five transcription factors (including two members of the steroid receptor superfamily), a TH-converting deiodinase, two metabolic enzymes, a protein disulfide isomerase-like protein that may bind TH, a neural-specific cytoskeletal protein, and two hypophysiotropic neuropeptides. This is the first successful attempt to isolate a large number of TH-target genes in the developing vertebrate brain. The gene identities allow predictions about the gene regulatory networks underlying TH action on the brain, and the cloned cDNAs provide tools for understanding the basic molecular mechanisms underlying neural cell differentiation.

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