A schematic representation of the 20E regulated events during the first vitellogenic cycle in the fat body of the mosquito <i>A. aegypti</i>.

<p>After a blood meal activation, a high level of 20E acts via EcRA/USPB heterodimer activating early genes, BrZ2, E74B and E75A, which synergistically activate late genes such as <i>Vg </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Chen1" target="_blank">[15]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Cruz1" target="_blank">[18]</a>. TOR, activated by amino acids and insulin, is essential for activating late genes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Hansen1" target="_blank">[3]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-GuliaNuss1" target="_blank">[6]</a>. TOR is also involved in inhibition of the programmed autophagy during vitellogenesis <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Bryant1" target="_blank">[19]</a>. HR3 is inhibited by E75A <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Cruz1" target="_blank">[18]</a>, but activated by EcRA/USPB ensuring its timely expression. At the termination time, lowering of the 20E titer results in repressive action of BriZ1 (not shown) and BrZ4 on late genes such as Vg <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Chen1" target="_blank">[15]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Zhu1" target="_blank">[17]</a>. In this study, we have shown that HR3 is involved in inhibition of late target genes expression (<i>Vg</i>). On the other hand, HR3 activates the EcRB/USPA heterodimer. EcR has been shown to repress TOR and activate autophagy <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Bryant1" target="_blank">[19]</a>. We postulate that it is the EcRB/USPA heterodimer that is responsible for these functions mediating action of HR3; however, this link requires additional confirmation. HR3 acts as an activator of betaFTZ-F1 that in turn is essential for maintaining cyclicity of egg development. The green ovals – EcR/USP 20E heterodimeric receptor; blue boxes – genes that encode 20E regulated transcription factors (early genes); purple boxes – Target-of Rapamycin; black boxes – autophagy; orange boxes – late target genes. Green arrows depict activating effects and red lines - repressive effects. The basics of the scheme were adapted from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045019#pone.0045019-Thummel1" target="_blank">[46]</a>for comparison reasons.</p>