A double negative post-transcriptional regulatory circuit mediates the virgin behavioral state

Summary from GEO:<br/><br/>"The survival and reproductive success of animals depends on the ability to harmonize their external behaviors with their internal states. For example, females conduct numerous social programs that are distinctive to virgins compared to post-mated and/or pregnant individuals. In Drosophila, the fact that the post-mating switch is initiated by seminal factors implies the default state as virgin. Recently, we uncovered molecular and genetic control of the female virgin state. In particular, repression of the transcription factor Homothorax (Hth) by mir-iab-4/8 within the abdominal ventral nerve cord (VNC) is critical for unmated females to execute virgin behaviors. To elucidate new components of this regulatory circuit, we exploited mir-iab-4/8 deletion and hth-miRNA binding site mutants (hth[BSmut]) to elucidate doublesex (dsx) as a critical downstream factor. While Dsx has mostly been studied during sex-specific differentiation, its activities in neurons are little known. We find that accumulation of Dsx in the CNS is mutually exclusive with Hth, and downregulated in miRNA/hth[BSmut] mutants. Moreover, experimental suppression of Dsx in highly restricted sets of abdominal neurons abrogates female virgin conducts, in favor of mated behavioral programs. Thus, a double negative pathway in the VNC mediates the virgin behavioral state."<br/> <br/>Overall design from GEO:<br/><br/>"RNA-seq from dissected Drosophila larvae VNC"

摘要自GEO：

动物之生存与繁殖成功，取决于其外部行为与其内部状态之间和谐统一的实现能力。例如，雌性动物会执行一系列独特的社交程序，这些程序与未交配个体相比，在已交配或/及怀孕个体中则表现出显著差异。在果蝇中，交配后切换机制的启动由精液因素触发，暗示了默认状态为未交配状态。近期，我们揭示了控制雌性未交配状态的分子和遗传机制。特别是，在腹部腹侧神经索（VNC）中，mir-iab-4/8对转录因子Homothorax（Hth）的抑制对于未交配雌性执行未交配行为至关重要。为了阐明此调控回路的新成分，我们利用mir-iab-4/8敲除株和hth-miRNA结合位点突变株（hth[BSmut]）来阐明doublesex（dsx）作为关键的下游因子。虽然Dsx主要在性别特异性分化过程中被研究，其在神经元中的活动知之甚少。我们发现，Dsx在中央神经系统（CNS）中的积累与Hth互斥，并且在miRNA/hth[BSmut]突变体中下调。此外，在腹部神经元高度受限的集合中实验性抑制Dsx，可消除雌性未交配行为，转而表现出交配行为程序。因此，VNC中的双重否定通路介导了未交配行为状态。

GEO的整体设计：

解剖果蝇幼虫腹部腹侧神经索的RNA测序