Biology Reference
In-Depth Information
cretinism in humans, lack of ligand causes striking neurological and bone
formation defects that can be explained by the deleterious effect of inappro-
priate gene regulation by the unliganded aporeceptor (
Bassett et al., 2007;
Chassande, 2003; Gothe et al., 1999
). Numerous studies analyzing the ef-
fects of hypothyroidism (largely in mammals) during embryogenesis have
shown that liganded TRs have numerous, essential roles in developmental
processes (see, for instance,
Escobar-Morreale, del Rey, Obregon, & de
Escobar, 1996
).
In
Xenopus laevis
,TR
a
and TR
b
are present at very low levels in the
oocyte, and then decrease and rise from NF24 stage (
Duarte-Guterman,
Langlois, Pauli, & Trudeau, 2010; Fini, Le M´vel, et al., 2012; Morvan
Dubois et al., 2006
); this stage of development corresponds to the matura-
tion of the nervous system (
Nieuwkoop & Faber, 1994
). TR
a
mRNA levels
then increase from hatching (NF35-37) to stage NF45, levels stabilizing at
stage NF48, prior to prometamorphosis (
Fini, Le M´vel, et al., 2012; Havis
et al., 2006; Morvan Dubois et al., 2006
). Generally, TR
b
was observed at
lower levels than TR
a
and was considered to be insignificant. However,
Havis et al. (2006)
showed that both TR
a
and TR
b
transcripts were present
at comparable levels and in that both displayed dynamic patterns of expres-
sion. More recently, we have revisited this question using qPCR and
showed that TR
b
mRNA levels are in fact slightly higher than those of
TR
a
mRNA in eggs but the two display similar expression profiles, with
the most marked increases occurring between stages NF37 and NF45
(
Fini, Le M´vel, et al., 2012; Havis et al., 2006
). Furthermore, the TR pro-
teins can be deduced to be functionally active well prior to metamorphosis,
as triiodothyronine (T
3
) treatment of stage 45 embryos induces precocious
metamorphosis (
Shi, Wong, Puzianowska-Kuznicka, & Stolow, 1996; Tata,
1968; Yaoita & Brown, 1990
). It is in fact this type of experiment, the ad-
dition of large amounts of T
3
to the stage 45 embryo, with the consequent,
but incomplete and disorganized, metamorphic-like response, that has
largely contributed to the perduring concept that apo-TRs have repressive
roles during early development. Some experimental work has addressed the
roles of unliganded receptor during
Xenopus
embryonic development.
Notably, using germinal transgenesis to overexpress a mutated TR that can-
not recruit corepressor complexes (nor coactivator complexes) allowed the
demonstration of the importance of unliganded TR
b
in craniofacial devel-
opment and particularly eye formation (
Havis et al., 2006
). In the same set of
experiments, the authors used a pharmacological approach to interfere with
TH signaling, the deiodinase inhibitor iopanic acid and the mixed TH
