Biology Reference
In-Depth Information
structures related to the visual system from E3.
Dio3
is in particular expressed
in the developing retina from E4 to E10 (
Geysens et al., 2012
).
Given their role in regulating ligand availability, deiodinases-like en-
zymes are also of interest in prochordates and their presence has been
characterized in numerous species, including Ciona (recently reviewed in
Darras & Van Herck, 2012
). Despite the apparently ubiquitous expression
of deiodinases during vertebrate development, the only cases where a devel-
opmental role has been formally demonstrated are the mouse models
describing
Dio3
and
Dio2
invalidation. If the individual global phenotypes
show surprisingly little alteration, these models demonstrate that certain
developmental processes are accelerated in the
Dio3
mutant, whereas
they are delayed in
Dio2
mutant (reviewed in
Galton, 2005; Williams &
Bassett, 2011
).
2.3. Transporters are expressed in embryonic tissues
TH transporters were cloned and characterized even later than deiodinases. It
had been assumed for a very long time that TH entered cells by passing
through membranes. However, in the 1970s, it was demonstrated that TH
uptake by cells is ATP-dependent and is therefore an active process (
Rao,
Eckel, Rao, & Breuer, 1976
). The demonstration that transporters are present
in the cytoplasmic membrane was not until two decades later (
Docter et al.,
1997
). Similarly for deiodinases, the properties of TH transport were analyzed
before the actual cloning of a transporter (see
Hennemann et al., 2001
for re-
view of transporter characteristics identified before cloning). The cloning of
the first transporter (i.e., MCT8) (
Friesema et al., 2003
) immediately opened
up a new field of research, a field that is increasingly active. Examination of
patients bearing a mutation in theMCT8 transporter led to the hypothesis that
the neurological damage was due to impaired TH availability in the develop-
ing brain,
therefore suggesting the importance of TH transporters
in
embryogenesis.
Recent experiments have described the expression of
MCT8
and
OATP1C1
in the developing chicken brain, suggesting that different brain
areas do not have the same TH requirements, in accordance with differences
in
Dio2
and
Dio3
expression (
Geysens et al., 2012; Van Herck et al., 2012
).
Nevertheless, no functional role has been demonstrated for these trans-
porters in chick brain up to now. The expression of mRNA encoding
MCT8 was also characterized in the zebrafish embryo, peaking at 48 h
postfertilization, which is consistent with its potential role in the control
