MicroRNA-Dependent Control of Sensory Neuron Function Regulates Posture Behavior in Drosophila

Abstract

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 behaviour and adaptation to the environment. Here we report that the evolutionarily-conserved microRNA (miRNA) miR-263b, plays a key behavioural 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 FACS-qPCR analysis -demonstrate miR-263b expression in larval sensory neurons. Second, behavioural tests in miR-263b null mutants show defects in self-righting, an innate and evolutionarily conserved posturecontrol behaviour 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 selfrighting defects. Fourth, systematic analysis of sensory neurons in miR-263b mutants shows no detectable morphological defects in their stereotypic pattern, whilst 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' behaviour and a compromised response to sound, both characteristic of larval sensory deficits. Furthermore, bioinformatic miRNA target analysis, gene expression assays, and behavioural phenocopy experiments suggest that miR-263b might exert its effects -at least in part -through repression of the bHLH transcription factor atonal. Altogether, our study suggests a model in which miRNA-dependent control of transcription factor expression affects sensory function and behaviour.

Noncoding RNAs: Emerging regulators of behavioral complexity

“…miRNA locus miR‐iab 4/8, along with the Hox gene Ultrabithorax, has been reported to affect the self‐righting behavior in the morphologically distinct larval as well as adult stages of Drosophila melanogaster (Issa et al, 2019; Picao‐Osorio et al, 2015). miRNAs also regulate many larval neuronal functions and dynamically complex male courtship behaviors in Drosophila (Iftikhar et al, 2019; Klann et al, 2021). Several studies report miRNAs, including miR‐323a, miR‐26a‐3p, miR‐34, miR‐135a, and miR‐101a, which target mRNAs functioning in different brain regions, affecting pathways culminating in anxiety or depression‐like symptoms in model organisms (Cohen et al, 2017; Fiori et al, 2021; Haramati et al, 2011; Li et al, 2021; Mannironi et al, 2018).…”

MicroRNAs in meningiomas: Potential biomarkers and therapeutic targets

“…MiRNA biogenesis begins with the processing of RNA polymerase II/III transcripts, occurring concurrently or post-transcriptionally [ [16] , [17] , [18] , [19] ]. A substantial number of miRNAs are derived from introns or specific protein-coding genes (intragenic), while others are intergenic, transcribed independently [ [20] , [21] , [22] , [23] ].…”

A microRNA that controls the emergence of embryonic movement

“…Recent work in our laboratory has shown that miRNAs -which are short regulatory non-coding RNAs that repress the expression of target genes [1,2] -have pervasive roles in the articulation of complex movement sequences such as those involved in body posture control in the young Drosophila larva [3][4][5][6]; these observations, as well as those from others in Drosophila and other systems [7][8][9][10][11] hinted at the possibility that these non-coding RNA molecules might also be involved in the control of more fundamental aspects of motor development and control. To explore this question, we first searched for miRNAs that might affect the simple locomotor patterns of the Drosophila first instar larva.…”