Rj. Denver et al., THYROID HORMONE-DEPENDENT GENE-EXPRESSION PROGRAM FOR XENOPUS NEURAL DEVELOPMENT, The Journal of biological chemistry, 272(13), 1997, pp. 8179-8188
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.