THYROID HORMONE-DEPENDENT GENE-EXPRESSION PROGRAM FOR XENOPUS NEURAL DEVELOPMENT

Although thyroid hormone (TH) plays a significant role in vertebrate n eural development, the molecular basis of TH action on the brain is po orly understood. Using polymerase chain reaction-based subtractive hyb ridization we isolated 34 cDNAs for TH-regulated genes in the dienceph alon of Xenopus tadpoles. Northern blots verified that the mRNAs are r egulated by TH and are expressed during metamorphosis. Kinetic analyse s showed that most of the genes are up-regulated by TH within 4-8 h an d 13 are regulated by TH only in the brain. All cDNA fragments were se quenced and the identities of seven were determined through homology w ith known genes; an additional five TH-regulated genes were identified by hybridization with known cDNA clones. These include five transcrip tion factors (including two members of the steroid receptor superfamil y), a TH-converting deiodinase, two metabolic enzymes, a protein disul fide isomerase-like protein that may bind TH, a neural-specific cytosk eletal protein, and two hypophysiotropic neuropeptides. This is the fi rst successful attempt to isolate a large number of TH-target genes in the developing vertebrate brain. The gene identities allow prediction s about the gene regulatory networks underlying TH action on the brain , and the cloned cDNAs provide tools for understanding the basic molec ular mechanisms underlying neural cell differentiation.