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In-Depth Information
dilp8
in tissues with abnormal growth prevents the delay in pupariation,
suggesting that it is required for the coupling of tissue growth and develop-
mental timing. Expression of
dilp8
in imaginal disks is also sufficient to delay
the onset of metamorphosis, which can be overcome by feeding larvae ec-
dysone (
Garelli et al., 2012
). Additionally, coculture experiments reveal that
ecdysone production in the ring gland is suppressed in response to Dilp8
produced by imaginal disks (
Colombani et al., 2012
). Taken together, these
results suggest that Dilp8 is secreted by the imaginal disks and remotely acts
on the ring gland to suppress ecdysone production and delay development.
How Dilp8 suppresses ecdysone is not known, but it may signal through the
InR pathway.
It has been shown that insulin signaling and ecdysone regulate each other
antagonistically (
Caldwell et al., 2005; Colombani et al., 2005; Mirth et al.,
2005
). A recent study has demonstrated a role for the nuclear cofactor,
dDOR, in the relationship between insulin signaling and ecdysone. They
show that dDOR is a coactivator of EcR, and that its expression is down-
regulated by insulin signaling via the inhibition of FOXO activity (
Francis,
Zorzano, & Teleman, 2010
). In addition, ecdysone induces translocation of
dFOXO into the nucleus, promoting
dDOR
expression, which further ac-
tivates EcR and initiates a feed-forward loop. Intriguingly,
dDOR
knockout
flies have a salivary gland degradation defect, and DOR has been shown to
regulate autophagy in both mammalian and
Drosophila
cells (
Francis et al.,
2010; Mauvezin et al., 2010
). These results provide one of the few clues
to how the relationship between insulin signaling, ecdysone, and autophagy
functions (
Fig. 4.3
).
4. AUTOPHAGY AND DROSOPHILA DEVELOPMENT
Most autophagy studies have been done using either yeast or mamma-
lian cell culture. While these studies have been essential to our understand-
ing of the genetic mechanisms that regulate autophagy, there is little known
about the impact of autophagy on the homeostasis of multicellular organ-
isms. It would be interesting to understand how autophagy in different cell
contexts, such as cell growth, cell survival, and cell death, affects the organ-
ism as a whole.
Drosophila
is an ideal system for studying autophagy in a multicellular
organism. The steroid and growth factor signaling pathways that regulate
autophagy are similar in flies and humans. Importantly,
Atg
genes and their reg-
ulators are highly conservedbetweenfliesandhumans(
Baehrecke, 2003
).
