Biology Reference
In-Depth Information
processes require cell proliferation, dividing disk cells presumably produce a
signal that suppresses ecdysone release. Consistent with this view, pupariation
is delayed in disk overgrowth mutants (
Sehnal & Bryant, 1993
). Importantly,
disk growth is determined by an autonomous genetic program that allows
them to stop their growth at a specific size even in culture conditions
(
Bryant & Levinson, 1985
). The preprogrammed target size thus functions
as a checkpoint that verifies that sufficient growth of disk tissue has occurred
before development can progress (
Fig. 1.2
).
Recently, two elegant genetic studies identified the elusive disk signal as
Dilp8, a molecule evolutionarily related to the insulin-like peptides
(
Colombani et al., 2012; Garelli et al., 2012
). Genetic manipulations that
(a) prolong the growth period before disks reach their correct target size,
(b) give rise to neoplastic disk growth, or (c) damage tissue all result in
upregulation of
Dilp8
expression. Reducing the expression of
Dilp8
does
not lead to premature pupariation which agrees with previous studies show-
ing that the disk signal is a permissive factor for developmental progression.
However, it is not clear how the Dilp8 signal converges on the endocrine
system to regulate ecdysone production or release. Potentially, it could work
either directly on the PG, through PTTH, or both to suppress ecdysone
production. Genetic disruption of disk growth mainly prolongs the duration
of the third instar (L3) up to 5 days (
Colombani et al., 2012
), similar to the
phenotype observed in larvae lacking either PTTH or its receptor Torso
(
McBrayer et al., 2007; Rewitz, Yamanaka, et al. 2009
). Like larvae with
reduced PTTH signaling, the second (L2) to L3 transition is only a few hours
delayed under conditions that affect disk growth (
Colombani et al., 2012
).
These observations suggest that Dilp8 prevents ecdysone production by
inhibition of PTTH signaling. This also agrees with the fact that disk dam-
age, like loss of PTTH, delays but does not prevent pupariation (
Colombani
et al., 2012; Garelli et al., 2012; Halme, Cheng, & Hariharan, 2010;
McBrayer et al., 2007; Rewitz, Yamanaka, et al. 2009
). Dilp8 may act at
one or more levels in the PTTH signaling pathway, including production
of PTTH, release of PTTH from varicosities on the PG, or by limiting
processing of PTTH to its active form. An alternative but not mutually
exclusive model is that Dilp8 may inhibit the capacity of the PG to respond
to PTTH, perhaps by affecting Torso production or activity. Based on an
earlier study which showed that disk damage reduces PTTH expression
in the PG neurons (
Halme et al., 2010
), it seems likely that Dilp8 acts at least
in part to suppress ecdysone production by downregulation of PTTH
synthesis in the PG neurons.
