Biology Reference
In-Depth Information
Embryogenesis
Premetamorphosis
Metamorphosis
T
3
RXR
a
T
4
100
75
50
TR
a
Hatching
Feeding
TR
b
25
1
35/36
45
51
55
58
61
63
66
Corepressor
complex
Coactivator
complex
TH response
gene expression
TR/RXR
TR/RXR
Histone deacetylation
& Gene repression
Chromatin remodeling
Histone acetylation/methylation
& Gene activation
Figure 10.1 A dual function model of TR in frog development. Top: Correlation of the
levels of endogenous TH and the mRNAs of TRa,TRb, and RXRa genes with develop-
ment in
. The embryos hatches around stage 35 and tadpole feeding begins
around stage 45 (
Nieuwkoop & Faber, 1956
). The plasma concentrations (arbitrary units)
of T
3
(crosses) and T
4
(open circles) are from
Leloup and Buscaglia (1977)
. The mRNA
levels for TRa (solid line), TRb (broken line), and RXRa (bold line) are based on published
data (
Wong & Shi, 1995; Yaoita & Brown, 1990
) and for clarity, plotted on arbitrary scales.
Bottom: Regulation of TH-inducible genes during frog development. TH-inducible
genes are expressed at the basal levels during embryogenesis when the levels of TH
and TRs are low. After tadpole feeding begins at stage 45, TRa and RXRa expression
increases dramatically. In the absence of the TH, the resulting TR-RXR heterodimers bind
to the TREs in the target genes and recruit corepressor complexes to repress gene
expression. After stage 55, the rise of endogenous TH concentration causes the release
of the corepressor complexes and recruitment of coactivator complexes to the pro-
moters due to its binding to TR. This leads to the activation of TH-inducible genes
and metamorphosis.
X. laevis
roles in their development (
Shi, 2013; Tata, 1993
). The most obvious and
earliest known abnormalities of human body and behavior associated with
TH-deficiency are goiter and cretinism (
Hetzel, 1989; Tata, 1993
). As in
amphibians, there is little TH in the embryonic plasma even though the thy-
roid gland is developed within the first 12 weeks of gestation in human
(
Hetzel, 1989; Howdeshell, 2002; Tata, 1993
). Significant TH production
