MicroRNA-Dependent Control of Sensory Neuron Function Regulates Posture Behavior in Drosophila.
MicroRNA-Dependent Control of Sensory Neuron Function Regulates Posture Behavior in Drosophila.
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微RNA依赖的感觉神经元功能控制调节果蝇的姿势行为。
DOI：
10.1523/jneurosci.0081-21.2021
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发表时间：
2021-10-06
期刊：
影响因子：
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通讯作者：
Alonso CR
中科院分区：
文献类型：
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作者：
Klann M;Issa AR;Pinho S;Alonso CR
我们所看到的、触摸到的、听到的、尝到的或闻到的一切，都必须首先由我们神经系统的感觉元件来检测。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。在这里，我们报告了进化保守的microRNA（miRNA）miR-263 b通过影响幼虫感觉神经元的功能在果蝇中起着关键的行为作用。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，通过报告基因表达和荧光激活细胞分选（FACS）-定量PCR（qPCR）分析的miRNA表达分析，证明了miR-263 b在幼虫感觉神经元中的表达。第二，miR-263 b无效突变体的行为测试显示了自我扶正的缺陷，这是一种先天的和进化上保守的姿势控制行为，如果颠倒过来，幼虫可以纠正自己的位置。第三，使用miR-263 b“海绵”竞争性抑制感觉神经元中的miR-263 b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 b无效突变体表现出减少的“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。总而言之，我们的研究提出了一个模型，其中转录因子表达的miRNA依赖性控制影响感觉功能和行为。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它们的特定特性还不清楚。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miRNA miR-263 b控制感觉神经元功能，使动物能够进行自适应的，精心制作的三维运动。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-263b plays a key behavioral role in Drosophila melanogaster through 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, demonstrate miR-263b expression in larval sensory neurons. Second, behavioral tests in miR-263b null 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 of miR-263b in sensory neurons using a miR-263b “sponge” leads to self-righting defects. Fourth, systematic analysis of sensory neurons in miR-263b mutants 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 in miR-263b mutants. Fifth, miR-263b null 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 that miR-263b might exert its effects, at least in part, through repression of the basic helix-loop-helix (bHLH) transcription factor Atonal. Altogether, our study suggests a model in which miRNA-dependent control of transcription factor expression affects sensory function and behavior. SIGNIFICANCE STATEMENT Sensory 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). Using Drosophila, we demonstrate that the evolutionarily-conserved miRNA miR-263b controls 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.