Biology Reference
In-Depth Information
complex for gene activation. Earlier studies have led us to propose a dual function
model for TR during development. In premetamorphic tadpoles, unliganded TR re-
presses transcription involving corepressors. During metamorphosis, endogenous T
3
al-
lows TR to activate gene expression. To fully understand the diversity of T
3
effects during
metamorphosis, whole genome analysis of transcriptome and mechanism of TR action
should be carried out. To this end, the new sequencing technologies have dramatically
changed how fundamental questions in biology are being addressed and is now mak-
ing the transition from technology development to being a standard for genomic and
functional genomic analysis. This review focuses on the applications of high-throughput
technologies to the field of amphibian metamorphosis.
1. INTRODUCTION
Amphibian development is marked by an indirect development. Em-
bryonic development and juvenile life style are separated by a larval period
(tadpole) that ends with metamorphosis. Metamorphosis is a switch that re-
sults in the reprogramming of the morphological and biochemical charac-
teristics of nearly all tadpole organs (
Shi, 1999
). Transformations involve
apoptosis of larval cells and concurrent proliferation and differentiation of
adult cell types. Although complex, metamorphosis is directly initiated by
thyroid hormone (TH) with 3,5,3
0
-triiodothyronine (T
3
) as the most bio-
logically active agent. Interestingly, this hormone-controlled developmental
phase shows strong similarities with the perinatal period in mammals, bird
hatching, and of course other kind of metamorphosis such as in fish and in-
sects (
Laudet, 2011
). Amphibian metamorphosis thus provides a powerful
model to analyze the essential roles for TH, notably in maturation of the ner-
vous system, the metabolism, the respiratory system, the intestine, and body
shape modification (
Shi, 1999; Tata, 1993
).
TH acts through thyroid hormone receptor (TR) that belongs to the
family of nuclear receptors (
Gronemeyer & Laudet, 1995
). TR is a transcrip-
tion factor that regulates gene expression by binding to DNA at specific sites
known as T
3
response elements (T
3
REs), mostly composed of two direct
repeats of the consensus sequence “AGGTCA” separated by four bases
(DR4). TH is a versatile player. It can not only upregulate, but also down-
regulate gene expression in target tissues or cells (
Flamant, Gauthier, &
Samarut, 2007
). Moreover, in the absence of TH, TR can also repress or
increase the transcription. As in mammals, there are two types of TR
(
a
and
b
) in amphibian (
Yaoita, Shi, & Brown, 1990
). Their amino acid se-
quences are well conserved in evolution and amphibian TR behaves
