A single microRNA-Hox gene module controls complex movement in morphologically-distinct developmental forms ofDrosophila

Abstract

Movement is the main output of the nervous system. It emerges during development to become a highly coordinated physiological process essential to the 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 these movements have a common or diverse molecular basis. Here we explore this problem in Drosophila focusing on the roles played by the microRNA (miRNA) locus miR-iab4/8 which was previously shown to be essential for the fruit fly larva to correct its orientation if turned upside down (self-righting) (Picao-Osorio et al., 2015). 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 behaviour in the Drosophila adult, an organism with radically different morphological and neural constitution. Through the combination of gene-expression, optical imaging and quantitative behavioural approaches we provide evidence that miR-iab4 exerts its effects on adult self-righting behaviour through repression of the Hox gene Ultrabithorax (Ubx) (Morgan, 1923;Sánchez-Herrero et al., 1985) in a specific set of motor neurons that innervate the adult Drosophila leg. Our results show that this miRNA-Hox module affects the function, rather than the morphology of motor neurons and indicate that postdevelopmental changes in Hox gene expression can modulate behavioural outputs in the adult.Altogether our work reveals that a common miRNA-Hox genetic module can control complex movement in morphologically-distinct organisms and describes a novel post-developmental role of the Hox genes in adult neural function.

A novel post-developmental role of the Hox genes underlies normal adult behaviour

“…Ubx is expressed in the adult ventral nerve cord (VNC) -the neural equivalent of the mammalian spinal cord ( 18) -across extensive domains on its dorsal and ventral aspects (Fig. 1A, and previous observations (3,10)). To probe specific expression within the dopaminergic system, we labelled the TH domain using nuclear GFP (NLS::GFP) under a dopaminergic driver (TH-Gal4) (Fig.…”

“…Further results indicate that flight-related dopaminergic activity takes place primarily within the VNC in segments T2-T3 (Fig. 4J), the thoracic regions where neural expression of Ubx is prominent (3,10). Expression of the CaLexA reporter within the intersectional domain THÇUbx reveals that even within this restricted aspect of the dopaminergic system, there are significant differences in CaLexA signal detected after flight, when compared with a resting control (Fig.…”

“…Amongst these factors, are the Hox genes, which encode a family of developmental factors whose activities control cell differentiation programs in animals as diverse as insects and mammals (5)(6)(7). Hox gene expression patterns have been studied in great detail during embryogenesis (8,9) but recent data from our laboratory and elsewhere (3,10) show that Hox genes are also expressed in adult forms (Figure 1A), yet, the biological roles of this late phase of expression are not known. We hypothesised that the Hox genes may contribute to the genetic programme underlying brain stability and used the Drosophila adult as a system to explore this notion, seeking to establish the biological roles of adult post-mitotic neural Hox gene expression.…”