Juvenile hormone regulates body size and perturbs insulin signaling in Drosophila

Abstract

The role of juvenile hormone (JH) in regulating the timing and nature of insect molts is well-established. Increasing evidence suggests that JH is also involved in regulating final insect size. Here we elucidate the developmental mechanism through which JH regulates body size in developing Drosophila larvae by genetically ablating the JH-producing organ, the corpora allata (CA). We found that larvae that lack CA pupariated at smaller sizes than control larvae due to a reduced larval growth rate. Neither the timing of the metamorphic molt nor the duration of larval growth was affected by the loss of JH. Further, we show that the effects of JH on growth rate are dependent on the forkhead box O transcription factor (FOXO), which is negatively regulated by the insulinsignaling pathway. Larvae that lacked the CA had elevated levels of FOXO activity, whereas a loss-of-function mutation of FOXO rescued the effects of CA ablation on final body size. Finally, the effect of JH on growth appears to be mediated, at least in part, via ecdysone synthesis in the prothoracic gland. These results indicate a role of JH in regulating growth rate via the ecdysone-and insulin-signaling pathways.T o correctly regulate their body size, animals control both the rate and duration of their growth. Canonically, growth rate and growth duration have been thought of as separate processes regulated by independent signaling pathways. In insects, the hormones ecdysone and juvenile hormone (JH) control the timing of the metamorphic transition and hence growth duration (1). The conserved insulin/insulin-like growth factor signaling (IIS) and target of rapamycin (TOR) pathways regulate growth rate (1). Recent evidence in Drosophila melanogaster indicates, however, that IIS and TOR signaling regulate ecdysone synthesis (2-5), whereas ecdysone antagonizes IIS (2, 6). This interaction between the mechanisms that regulate growth duration and those that control growth rate appears to coordinate the two processes, and may be a general feature of size regulation. To test this hypothesis, we explored whether JH also regulates growth rate in Drosophila.In the tobacco hornworm Manduca sexta, JH regulates growth duration by regulating the hormonal response to critical weight, a size checkpoint used to determine when to end growth and begin metamorphosis (7). A decline in circulating JH initiates the first step in the hormonal cascade that begins with attainment of critical weight, and ends, after a terminal growth period (TGP), in the rise in circulating ecdysone that stops body growth (8-10). Starvation maintains high rates of JH synthesis in the JH-producing tissue, the corpora allata (CA) (9), and delays the critical weight transition (8). Removal of the CA (CAX) causes larvae to reach critical weight earlier than normal and at a smaller size (8, 11). Application of JH suppresses the critical weight transition and delays metamorphosis, resulting in larger size (8).Intriguingly, recent studies show that, like CAX Manduca, CAX Drosophila larvae are smaller ...

A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3

“…Treatment to control tub>dilp8 C150A animals that display normal pupation time (12) did not increase their size above that of their untreated siblings (Fig. 6D, right) and (44). We conclude that reduced JH signaling lessen larval growth contributing to ensuing normal sized tub>dilp8 animals (Fig.…”

Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator

“…Upon exposure to 20E, Eip74EF/Eip75B expression levels increase dramatically, whereas InR levels increase much more modestly (Fig. S13) (Bernardo et al, 2014;Mirth et al, 2014). The incoherent feed-forward properties of the InR gene, with simultaneous positive and negative effects, might ensure more precise changes in gene expression, preventing pleiotropic impacts Dashed lines indicate elements that are active in a cell type-specific manner.…”

Glue protein production can be triggered by steroid hormone signaling independent of the developmental program in Drosophila melanogaster

“…JH is involved in the assessment of nutritional status and determination of final body size (Nijhout and Williams, 1974b; Mirth et al, 2014). Further, the antagonistic action of JH against the acceleration of metamorphic timing caused by ecdysteroids has been reported (Ono, 2014).…”