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to the TH target genes to repress their expression and thus prevent organ
metamorphosis. Thus, there is likely a tissue-specific critical ratio of liganded
to unliganded TR that determines the timing of organ metamorphosis.
6. CONCLUSIONS
Anuran metamorphosis is one of the most dramatic events regulated
by TH. It is tightly controlled during development both on the timing
of the initiation of this process at whole animal level and on the temporal
coordination of organ-specific transformations. The biosynthesis of endog-
enous TH and the regulation of cellular free TH levels are the key deter-
minants controlling the timing of metamorphosis. Mechanistically, the
metamorphic effect of TH is mediated by TR through regulating the tran-
scription of TH-target genes. Low levels of TH ensure a high fraction of
TR in the unliganded state at the target genes. This leads to the recruitment
of HDAC-containing corepressor complexes to repress the genes, thus
preventing the onset of animal metamorphosis and organ transformations.
During metamorphosis, high levels of TH lead to liganded TR that activates
target gene transcription to induce metamorphosis. Such a ligand switch
behavior controls the impressive morphological development of the frog.
ACKNOWLEDGMENT
The work in the author's laboratory has been supported by the Intramural Research Program
of NICHD, NIH.
REFERENCES
Barsano, C. P., & Groot, L.
(1983). Nuclear cytoplasmic interrelationships.
In
J. Oppenheimer & H. Samuels
(Eds.),
Molecular basis of
thyroid hormone action
