A Single MicroRNA-Hox Gene Module Controls Equivalent Movements in Biomechanically Distinct Forms of Drosophila
A Single MicroRNA-Hox Gene Module Controls Equivalent Movements in Biomechanically Distinct Forms of Drosophila
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DOI：
10.1016/j.cub.2019.06.082
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发表时间：
2019-08-19
期刊：
影响因子：
9.2
通讯作者：
Alonso, Claudio R.
中科院分区：
文献类型：
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作者：
Issa, A. Raouf;Picao-Osorio, Joao;Alonso, Claudio R.
运动是神经系统的主要输出。它在发育过程中出现，成为生物体生存和适应环境所必需的高度协调的生理过程。在形态上不同的有机体发育阶段也可以观察到类似的运动，但目前尚不清楚这些运动是否具有共同的分子细胞基础。在这里，我们在果蝇中探索这个问题，重点是microRNA(MiRNA)基因座miR-iab4/8所扮演的角色，我们先前证明，当果蝇幼虫颠倒(自我扶正)时，该基因对于果蝇幼虫的正常纠正反应是必不可少的。我们的研究表明，miR-iab4是所有三个果蝇幼虫正常自我扶正所必需的。出乎意料的是，我们还发现这种miRNA对于成年苍蝇的正常自我扶正行为是必不可少的，成年苍蝇是一个具有不同形态、神经构成和生物力学的有机体。通过基因表达、光学成像和定量行为方法的结合，我们提供了证据，表明miR-iab4部分通过抑制一组特定的成年运动神经元-NB2-3/lin15神经元中的Hox基因Ultrabithorax(UBx)来影响成人的自我扶正行为。我们的结果表明，miRNA控制这些神经元的功能，而不是形态，并证明发育后HOX基因表达的变化可以调节成年人的行为。我们的工作揭示了一个共同的miRNA-HOX基因模块可以在不同的神经元中重新部署，以控制在生物力学上不同的生物体中功能相同的运动，并描述了HOX基因在成年神经功能中的一种新的发育后角色。
Movement is the main output of the nervous system. It emerges during development to become a highly coordinated physiological process essential to survival and adaptation of the organism to the environment. Similar movements can be observed in morphologically distinct developmental stages of an organism, but it is currently unclear whether or not these movements have a common molecular cellular basis. Here we explore this problem in Drosophila, focusing on the roles played by the microRNA (miRNA) locus miR-iab4/8, which we previously showed to be essential for the normal corrective response displayed by the fruit fly larva when turned upside down (self-righting). Our study shows that miR-iab4 is required for normal self-righting across all three Drosophila larval stages. Unexpectedly, we also discover that this miRNA is essential for normal self-righting behavior in the adult fly, an organism with different morphology, neural constitution, and biomechanics. Through the combination of gene expression, optical imaging, and quantitative behavioral approaches, we provide evidence that miR-iab4 exerts its effects on adult self-righting behavior in part through repression of the Hox gene Ultrabithorax (Ubx) in a specific set of adult motor neurons, the NB2-3/lin15 neurons. Our results show that miRNA controls the function, rather than the morphology, of these neurons and demonstrate that post-developmental changes in Hox gene expression can modulate behavior in the adult. Our work reveals that a common miRNA-Hox genetic module can be re-deployed in different neurons to control functionally equivalent movements in biomechanically distinct organisms and describes a novel post- post-developmental role of the Hox genes in adult neural function.