Abstract

SummaryMovement 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-developmental role of the Hox genes in adult neural function.

Highlights

  • Through the combination of gene expression, optical imaging, and behavioral analyses, we show that a single genetic module composed of the miRNA miR-iab4 and the Hox gene Ubx contributes to the SR response in both Drosophila larvae and adults

  • To investigate whether miR-iab4/8-dependent effects were confined to the L1 stage or had impact throughout larval development, we conducted a series of SR tests in first, second, and third instar larvae (L1, L2, and L3 larvae, respectively) (Figures 1A and 1B)

  • SR was assayed by briefly putting individuals upside down and monitoring the time they took to come back to a normal right-side up position (STAR Methods). miRNA mutant larvae take longer to complete the SR sequence (Figure 1C), indicating that this miRNA system is important for the normal timing of the SR response across all three larval stages

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Summary

Introduction

In principle, following the ‘‘Brenner paradigm’’ [6], genetic mutations could affect the control of movement in two fundamentally distinct ways: they could impair the developmental formation of the networks underlying movement control or interfere with the function of the cellular components involved in the physiological regulation of movement. These two levels of action of the genetic system need not be mutually exclusive (see below)

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