Biology Reference
In-Depth Information
mechanisms, the synthesis of endogenous TH appears to dictate the timing
of metamorphosis initiation.
On the other hand, metamorphosis can be precociously induced in
premetamorphic tadpoles as early as at stage 41 for
X. laevis
, only 3 days after
fertilization, by the treatment with exogenous TH, while younger tadpoles
or embryos are resistant to TH (
Shi, 1999; Tata, 1968
). Thus,
Xenopus
tad-
poles gain competence to respond to TH as early as stage 41, much earlier
than the onset of metamorphosis at stage 55. In addition, different organs
undergo metamorphosis at distinct developmental stages even though
they are exposed to the same circulating plasma TH. Studies over the last
two decades have demonstrated a critical role of TH receptor (TR) in both
mediating the metamorphic effect of TH and ensuring proper growth and
development of different tadpole organs prior to metamorphosis.
2. TR FUNCTION DURING FROG DEVELOPMENT
TH affects development mainly by regulating gene expression
through TRs, although non-genomic effects of TH have also been docu-
mented (
Buchholz, Paul, Fu, & Shi, 2006; Davis & Davis, 1996; Evans,
1988; Lazar, 1993; Tsai & O'Malley, 1994; Yen, 2001
). There are two evo-
lutionary conserved TR genes, TR
a
and TR
b
, in all vertebrate species
and both are members of the nuclear hormone receptor superfamily
(
Laudet & Gronemeyer, 2002
). TRs can bind to TH response elements
(TREs) as monomers, homodimers, as well as heterodimers formed with
9-cis-retinoic acid receptors (RXRs), also members of the superfamily.
TH can both activate and repress gene expression. TH-inducible genes,
TR-RXR heterodimers bind to TREs in/around the promoters of target
genes even in the context of chromatin and repress their expression in
the absence of TH. TH-binding to TR leads to chromatin disruption and
the activation of these promoters (
Hsia & Shi, 2002; Hsia, Wang, & Shi,
2001; Shi, Matsuura, Fujimoto, Wen, & Fu, 2012; Wong et al., 1998;
Wong, Shi, & Wolffe, 1995, 1997
).
TR regulates transcription by recruiting cofactor complexes to target
genes. In the absence of TH, TR recruits corepressor complexes, such as
those containing histone deacetylase histone deacetylase 3 (HDAC3) and
the highly related TR-binding proteins N-CoR and SMRT (
Burke &
Baniahmad, 2000; Glass & Rosenfeld, 2000; Guenther et al., 2000;
Ishizuka & Lazar, 2003; Jones, Sachs, Rouse, Wade, & Shi, 2001;
Jones & Shi, 2003; Li, Wang, et al., 2000; Shi et al., 2012; Yoon et al.,
