Biology Reference
In-Depth Information
prothoracic gland via binding to heme? This concept is based on the idea
that
b
FTZ-F1 regulates ecdysone biosynthesis, as it was shown that sim-
ilar to its vertebrate homolog SF-1,
b
FTZ-F1 also has critical roles in the
regulation steroidogenic genes (
Broadus et al., 1999; Parker & Schimmer,
1997; Parvy et al., 2005; Yamada et al., 2000
). SF-1 expression is re-
stricted to steroidogenic tissues in mice, and the protein controls the ex-
pression of several steroid hydroxylase genes. Likewise,
b
FTZ-F1 was
shown to regulate the expression of at least two ecdysone biosynthetic
enzymes, Phantom and Disembodied, in prothoracic gland cells (
Parvy
et al., 2005
)(
Fig. 2.4
B).
Several lines of evidence support the idea that NO signaling modulates
the DHR3/E75-mediated regulation of
b
FTZ-F1, which would in turn af-
fect ecdysone production (
Caceres et al., 2011
). First, the
NOS
RNAi
knockdown in prothoracic glands results in a failure to induce the expression
of
b
ftz-f1
, consistent with the idea that the late third instar ecdysone peak
relies on proper
b
ftz-f1
upregulation. Second,
b
ftz-f1
expression can be re-
stored by either providing a constitutively active form of the NOS enzyme
in vivo
or by coculturing ring glands with an NO donor
in vitro
. These data
strongly suggest that NO is sufficient to activate
b
ftz-f1
expression at this
time in development. Third, the inhibition of DHR3 activity by E75 bind-
ing can be reversed by NO. Taken together, the report by Caceres and col-
leagues proposes a novel mechanism by which ecdysteroidogenesis is
controlled in the
Drosophila
prothoracic gland. To further consolidate this
model, one could determine whether a ring gland-specific knockdown of
b
ftz-f1
results in low ecdysone titers, and whether the expression or
upregulation of the two reported
b
FTZ-F1 targets,
phantom
and
disembodied
,
are abolished in the absence of NO signaling.
It is of interest to note that the prothoracic gland-specific knockdown of
NOS
triggers a massive overgrowth of the ring gland. NO is a well-known
regulator of cell proliferation (
Villalobo, 2006
), which raises the interesting
question as to whether this overgrowth phenotype is due to an increase in
cell number or cell size. The
Drosophila
ring gland cells undergo
endoreplication where the cell number is determined during embryogene-
sis, which appears to be consistent with the idea that NO acts as a negative
effector of cell growth. However, it was recently suggested that DHR3 plays
a role in maintaining cell-autonomous growth (
Montagne et al., 2010;
Villalobo, 2006
), raising the possibility that hyperactivation of DHR3 due
to low NO levels could contribute to the overgrowth of the gland in
NOS
RNAi animals.
