The Corazonin-PTTH Neuronal Axis Controls Systemic Body Growth by Regulating Basal Ecdysteroid Biosynthesis in Drosophila melanogaster
The Corazonin-PTTH Neuronal Axis Controls Systemic Body Growth by Regulating Basal Ecdysteroid Biosynthesis in Drosophila melanogaster
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DOI：
10.1016/j.cub.2020.03.050
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发表时间：
2020-06-08
期刊：
影响因子：
9.2
通讯作者：
Niwa, Ryusuke
中科院分区：
文献类型：
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作者：
Imura, Eisuke;Shimada-Niwa, Yuko;Niwa, Ryusuke
类固醇激素在各种动物门的发育，生长和繁殖中起着关键作用[1]。昆虫类固醇激素蜕皮激素协调生长和成熟，以蜕皮和变态为代表[2]。在黑腹果蝇中，产生促前胸腺激素（PTTH）的神经元刺激蜕皮类固醇生物合成的峰值水平以使其成熟[3]。此外，最近关于PTTH信号传导的研究表明，蜕皮激素的基础水平对成熟前的全身生长产生负面影响[4-8]。然而，目前还不清楚PTTH信号是如何调节基础蜕皮甾类生物合成。在这里，我们报告，Corazonin（Crz）生产神经元调节基础蜕皮激素的生物合成影响PTTH神经元。Crz属于促性腺激素释放激素（GnRH）超家族，这意味着在生长和成熟中具有类似的作用[9]。抑制Crz神经元的活动增加蛹的大小，而它几乎不影响pupariation时间。这种表型是由于在三龄幼虫中期（L3）阶段的增长速度加快和蜕皮激素水平升高延迟。有趣的是，Crz受体（CrzR）在PTTH神经元中的表达在中期高于晚期L3阶段。PTTH神经元中CrzR的沉默增加了蛹的大小，表现为Crz神经元活性的抑制。当Crz神经元被光遗传学激活时，在L3中期的PTTH神经元中观察到强烈的钙反应，但在L3晚期则没有。此外，我们发现，章鱼胺神经元接触Crz神经元在食管下区（SEZ），传递信号的全身生长。总之，我们的研究结果表明，Crz-PTTH神经元轴调节蜕皮激素的生物合成响应章鱼胺，揭示了从生长到成熟的发育过渡中的调节神经内分泌系统。
Steroid hormones play key roles in development, growth, and reproduction in various animal phyla [1]. The insect steroid hormone, ecdysteroid, coordinates growth and maturation, represented by molting and metamorphosis [2]. In Drosophila melanogaster, the prothoracicotropic hormone (PTTH)-producing neurons stimulate peak levels of ecdysteroid biosynthesis for maturation [3]. Additionally, recent studies on PTTH signaling indicated that basal levels of ecdysteroid negatively affect systemic growth prior to maturation [4-8]. However, it remains unclear how PTTH signaling is regulated for basal ecdysteroid biosynthesis. Here, we report that Corazonin (Crz)-producing neurons regulate basal ecdysteroid biosynthesis by affecting PTTH neurons. Crz belongs to gonadotropin-releasing hormone (GnRH) superfamily, implying an analogous role in growth and maturation [9]. Inhibition of Crz neuronal activity increased pupal size, whereas it hardly affected pupariation timing. This phenotype resulted from enhanced growth rate and a delay in ecdysteroid elevation during the mid-third instar larval (L3) stage. Interestingly, Crz receptor (CrzR) expression in PTTH neurons was higher during the mid-than the late-L3 stage. Silencing of CrzR in PTTH neurons increased pupal size, phenocopying the inhibition of Crz neuronal activity. When Crz neurons were optogenetically activated, a strong calcium response was observed in PTTH neurons during the mid-L3, but not the late-L3, stage. Furthermore, we found that octopamine neurons contact Crz neurons in the subesophageal zone (SEZ), transmitting signals for systemic growth. Together, our results suggest that the Crz-PTTH neuronal axis modulates ecdysteroid biosynthesis in response to octopamine, uncovering a regulatory neuroendocrine system in the developmental transition from growth to maturation.