microRNA-dependent control of sensory neuron function regulates posture behaviour in Drosophila
microRNA-dependent control of sensory neuron function regulates posture behaviour in Drosophila
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感觉神经元功能的 microRNA 依赖性控制调节果蝇的姿势行为
DOI：
10.1101/2020.08.24.262626
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Klann M
中科院分区：
文献类型：
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作者：
Klann M
我们所看到、触摸到、听到、尝到或闻到的所有东西都必须首先被我们神经系统的感觉元件检测到。因此，感觉神经元是所有神经回路中的关键组成部分，它们的正确功能对于行为的产生和对环境的适应至关重要。在此，我们报道了进化保守的microRNA（miRNA）miR-263 b通过影响果蝇幼虫感觉神经元的功能在果蝇中发挥关键的行为作用。几个独立的实验（在50：50的男性：女性群体中）支持这一发现：首先，miRNA表达分析，通过报告基因表达和荧光激活细胞分选（FACS）-定量PCR（qPCR）分析，证明miR-263 b在幼虫感觉神经元中表达。第二，对miR-263 b无效突变体的行为测试显示出自我扶正的缺陷，这是一种先天的和进化上保守的姿势控制行为，允许幼虫在倒置时纠正它们的位置。第三，使用amiR-263 b“海绵”竞争性抑制miR-263 bin感觉神经元导致自扶正缺陷。第四，对miR-263 b突变体中感觉神经元的系统分析显示，在其刻板模式中没有可检测到的形态学缺陷，而在感觉结构域中表达的遗传编码的钙传感器揭示了miR-263 b突变体中神经活性的降低。第五，miR-263 bnull突变体表现出降低的“触摸反应”行为和对声音的妥协反应，这两者都是幼虫感觉缺陷的特征。此外，生物信息学miRNA靶标分析、基因表达测定和行为表型实验表明，miR-263 b可能至少部分通过抑制碱性螺旋-环-螺旋（bHLH）转录因子Atonal发挥其作用。总之，我们的研究提出了一个模型，在该模型中，转录因子表达的miRNA依赖性控制影响感觉功能和behaviors.Significance声明感觉神经元是神经回路功能的关键，但这些神经元如何获得其特定的属性还没有得到很好的理解。在这里，我们研究这个问题，重点是microRNAs（miRNAs）所扮演的角色。使用果蝇，我们证明了进化上保守的miRNAmiR-263 b控制感觉神经元功能，使动物能够进行适应性的，复杂的三维运动。因此，我们的工作表明microRNA可以通过调节感觉神经元生理学来控制复杂的运动行为，并表明类似的miRNA依赖机制可能在其他物种中起作用。这项工作有助于促进对行为的分子基础和microRNA在神经系统中的生物学作用的理解。
All what we see, touch, hear, taste, or smell must first be detected by the sensory elements of our nervous system. Sensory neurons, therefore, represent a critical component in all neural circuits and their correct function is essential for the generation of behavior and adaptation to the environment. Here, we report that the evolutionarily-conserved microRNA (miRNA)miR-263bplays a key behavioral role inDrosophila melanogasterthrough effects on the function of larval sensory neurons. Several independent experiments (in 50:50 male:female populations) support this finding: first, miRNA expression analysis, via reporter expression and fluorescent-activated cell sorting (FACS)-quantitative PCR (qPCR) analysis, demonstratemiR-263bexpression in larval sensory neurons. Second, behavioral tests inmiR-263bnull mutants show defects in self-righting, an innate and evolutionarily conserved posture-control behavior that allows larvae to rectify their position if turned upside-down. Third, competitive inhibition ofmiR-263bin sensory neurons using amiR-263b“sponge” leads to self-righting defects. Fourth, systematic analysis of sensory neurons inmiR-263bmutants shows no detectable morphologic defects in their stereotypic pattern, while genetically-encoded calcium sensors expressed in the sensory domain reveal a reduction in neural activity inmiR-263bmutants. Fifth,miR-263bnull mutants show reduced “touch-response” behavior and a compromised response to sound, both characteristic of larval sensory deficits. Furthermore, bioinformatic miRNA target analysis, gene expression assays, and behavioral phenocopy experiments suggest thatmiR-263bmight exert its effects, at least in part, through repression of the basic helix-loop-helix (bHLH) transcription factorAtonal. Altogether, our study suggests a model in which miRNA-dependent control of transcription factor expression affects sensory function and behavior.SIGNIFICANCE STATEMENTSensory neurons are key to neural circuit function, but how these neurons acquire their specific properties is not well understood. Here, we examine this problem, focusing on the roles played by microRNAs (miRNAs). UsingDrosophila, we demonstrate that the evolutionarily-conserved miRNAmiR-263bcontrols sensory neuron function allowing the animal to perform an adaptive, elaborate three-dimensional movement. Our work thus shows that microRNAs can control complex motor behaviors by modulating sensory neuron physiology, and suggests that similar miRNA-dependent mechanisms may operate in other species. The work contributes to advance the understanding of the molecular basis of behavior and the biological roles of microRNAs within the nervous system.