Biology Reference
In-Depth Information
POSITIVE
NEGATIVE
Prothoracic gland
Peripheral tissues
Ecdysone
Ecdysone
EcR
Feed
forward
loop
Feedback
loop
Cyp18
Ecdysonoic
acid
EcR
EcR
E23
Figure 1.4 Feedback control shapes the ecdysone pulses. A short positive and a long
negative feedback loop are believed to operate in the PG to control synthesis of ecdy-
sone. The short positive feedforward loop presumably amplifies the ecdysone signal
causing a fast increase of the titer. On the other hand, a long negative feedback loop
shuts off the PG which allows peripheral mechanisms to clear ecdysone from the sys-
tem. Ecdysone induces two feedback mechanisms, in tissues peripheral to the PG, which
are eventually responsible for lowering cellular levels (E23) and the decline of the titer
(Cyp18). Ecdysone induces Cyp18 that eliminates ecdysone by converting it into the in-
active ecdysonoic acid. The ecdysone-inducible E23 encodes an ABC transporter
believed to pump ecdysone out of the cells. Together these feedback mechanisms
determine the duration of the ecdysone pulses.
O'Connor, 2011
), such feedback regulation makes intuitive sense and the
physiological significance awaits further investigations.
Feedback control of PG activity through EcR may involve other
ecdysone-inducible genes required for the ecdysone response in peripheral tis-
sues. It is interesting to note that in a recent study DHR4, previously charac-
terized as an ecdysone-inducible gene, was shown to be necessary to control
the duration of the ecdysone pulses (
King-Jones, Charles, Lam, & Thummel,
2005; Ou et al., 2011; Rewitz & O'Connor, 2011
). When located in the nu-
cleus, DHR4 represses ecdysone production, which helps establish the dura-
tion of the ecdysone pulses. Although PTTH-regulated nucleocytoplasmic
shuttling of the DHR4 protein could account for this, the rapid effect of
DHR4 RNAi argues that there is more to this than simple shuttling of a stable
