Egfr Signaling Is a Major Regulator of Ecdysone Biosynthesis in the Drosophila Prothoracic Gland
Egfr Signaling Is a Major Regulator of Ecdysone Biosynthesis in the Drosophila Prothoracic Gland
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DOI：
10.1016/j.cub.2020.01.092
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发表时间：
2020-04-20
期刊：
影响因子：
9.2
通讯作者：
Franch-Marro, Xavier
中科院分区：
文献类型：
--
作者：
Cruz, Josefa;Martin, David;Franch-Marro, Xavier
了解决定动物最终身体大小的机制是生物学的一个中心问题。在具有确定生长的动物中，如哺乳动物或昆虫，未成熟生物体转化为成年生物体的大小决定了最终的身体大小，因为成年个体不会生长[1]。在果蝇中，当未成熟的幼虫经历变态转变以发育成成熟的成虫时，生长期结束[2]。这种变态转变是由前胸腺（PG）中合成的类固醇蜕皮激素急剧增加引发的，发生在三龄幼虫（L3）结束时[3-6]。人们普遍认为，果蝇中蜕皮激素的生物合成主要是由两对神经分泌细胞产生的促前胸腺激素（Ptth）激活酪氨酸激酶（RTK）诱导的，这些细胞将其轴突投射到PG上[7，8]。然而，Ptth和躯干缺失突变动物都不能阻止幼虫发育，而只是延迟了幼虫-蛹转变[9-11]，这一事实要求重新考虑传统模型。在这里，我们表明，Egfr信号，而不是Ptth/躯干，是在果蝇蜕皮激素生物合成的主要贡献者。我们发现，表皮生长因子受体信号被激活的PG中的自分泌模式的EGF配体斯皮茨和静脉，这反过来又调节的蜕皮激素的水平。这种调节性正反馈回路确保蜕皮激素的产生，以通过MAPK/ERK途径的渐进性Egfr依赖性激活来触发变态，从而决定动物最终的体型。
Understanding the mechanisms that determine final body size of animals is a central question in biology. In animals with determinate growth, such as mammals or insects, the size at which the immature organism transforms into the adult defines the final body size, as adult individuals do not grow [1]. In Drosophila, the growth period ends when the immature larva undergoes the metamorphic transition to develop the mature adult [2]. This metamorphic transition is triggered by a sharp increase of the steroid ecdysone, synthetized in the prothoracic gland (PG), that occurs at the end of the third instar larvae (L3) [3-6]. It is widely accepted that ecdysone biosynthesis in Drosophila is mainly induced by the activation of tyrosine kinase (RTK) Torso by the prothoracicotropic hormone (Ptth) produced into two pairs of neurosecretory cells that project their axons onto the PG [7, 8]. However, the fact that neither Ptth nor torso-null mutant animals arrest larval development but only present a delay in the larva-pupa transition [9-11] mandates for a reconsideration of the conventional model. Here, we show that Egfr signaling, rather than Ptth/torso, is the major contributor of ecdysone biosynthesis in Drosophila. We found that Egfr signaling is activated in the PG in an autocrine mode by the EGF ligands spitz and vein, which in turn are regulated by the levels of ecdysone. This regulatory positive feedback loop ensures the production of ecdysone to trigger metamorphosis by a progressive Egfr-dependent activation of MAPK/ERK pathway, thus determining the animal final body size.