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such as E75, DHR3, and
b
FTZ-F1, are also involved in the production of
ecdysone in the PG (
Caceres et al., 2011; Parvy et al., 2005
). Although little
is known about the factors involved in the transcriptional regulation of the
Halloween genes,
b
FTZ-F1 is required for expression of the genes
phantom
and
disembodied
(
Parvy et al., 2005
). Expression of
b
FTZ-F1
requires activa-
tion by DHR3, which is repressed by E75. Activity of the NO synthase
(NOS), catalyzing the production of NO, is required for NO-mediated in-
hibition of E75 activity in the PG (
Caceres et al., 2011
). Reducing expres-
sion of NOS in the PG results in a failure to produce ecdysone and an
inability to undergo metamorphosis. These larvae have enlarged PG cells
with increased endoreplication number, consistent with the view that in-
creased PG cell size alone is not sufficient for high level ecdysone production
(
Colombani et al., 2005
). Together, these results show that NO signaling has
an essential role in the regulation of ecdysone production that controls de-
velopmental transitions, although the mechanism regulating NO signaling
in the PG remains unknown.
In addition toNO, recentwork in
Drosophila
has shown thatTGF
b
/Activin
signaling is essential for ecdysone synthesis and developmental transitions
(
Gibbens et al., 2011
). Interestingly, TGF
b
and insulin signaling also
converge in
Caenorhabditis elegans
on the synthesis of the steroid hormone
dafachronic acid (DA), which interacts with the nuclear receptor DAF-12 to
determine whether larvae undergo reproductive development or arrest in a
dauer state (
Tennessen & Thummel, 2011
). In
Drosophila
, reduced TGF
b
/
Activin signaling in the PG, mediated by knockdown of
dSmad2
, the major
downstreammediator of TGF
b
signals, causes developmental arrest in the third
instar (
Gibbens et al., 2011
). Disrupting TGF
b
/Activin reduces expression of
torso
and the
InR
in the PG, presumably blocking the ability to synthesize ec-
dysone in response to PTTH and insulin. Moreover, restoring Torso/MAPK
or InR/Akt in the PG rescues the phenotype of
dSmad2
-RNAi knockdown.
Interestingly, resupplying the insulin receptor in the PGof larvaewith reduced
PG expression of
dSmad2
restores protein, but not transcript levels, of key ec-
dysone biosynthetic enzymes. Conversely, activating Torso/Ras signaling in
the PG of these larvae rescues the reduced expression of these genes. Thus, po-
tentially insulin and PTTH regulate the ecdysone biosynthetic machinery by
distinctmechanisms onevia transcriptionand theother via translational control.
Together, these observations indicate that TGF
b
/Activin signaling is impor-
tant for the PG to develop competence to respond to additional developmental
(PTTH) and nutritional (insulin) cues. Presently, it is not known whether
TGF
b
/Activin signaling is developmentally regulated to provide stage-specific
