The relationship between microRNA regulation and the specification of behaviour is only beginning to be explored. Here we find that mutation of a single microRNA locus (miR-iab4/8) in Drosophila larvae affects the animal' s capacity to correct its orientation if turned upside-down (self-righting). One of the microRNA targets involved in this behaviour is the Hox gene Ultrabithorax whose derepression in two metameric neurons leads to self-righting defects. In vivo neural activity analysis reveals that these neurons, the self-righting node (SRN), have different activity patterns in wild type and miRNA mutants whilst thermogenetic manipulation of SRN activity results in changes in self-righting behaviour. Our work thus reveals a microRNA-encoded behaviour and suggests that other microRNAs might also be involved in behavioural control in Drosophila and other species.The regulation of RNA expression and function is emerging as a hub for gene expression control across a variety of cellular and physiological contexts including neural development and specification. Small RNAs such as microRNAs (miRNAs) have been shown to affect neural differentiation (1, 2) but their roles in the control of behaviour are only beginning to be explored.Previous work in our laboratory focused on the mechanisms and impact of RNA regulation on the expression and neural function of the Drosophila Hox genes (3-6). These genes encode a family of evolutionarily conserved transcription factors that control specific programs of neural differentiation along the body axis (7-9) offering an opportunity to investigate how RNA regulation relates to the formation of complex tissues such as the nervous system.Here we use the Hox gene system to investigate the roles played by a single miRNA locus (miR-iab4/8) (3,(10)(11)(12)(13)(14)30) on the specification of the nervous system during early Drosophila development. This miRNA locus controls the embryonic expression of posterior Hox genes (3,(10)(11)(12)(13)(14). Given that we found no detectable differences in the morphological layout of the main components of the nervous system in late Drosophila embryos of wild + This manuscript has been accepted for publication in Science. This version has not undergone final editing. Please refer to the complete version of record at http://www.sciencemag.org/. The manuscript may not be reproduced or used in any manner that does not fall within the fair use provisions of the Copyright Act without the prior, written permission of AAAS. * Correspondence to: Claudio R. Alonso c.alonso@sussex.ac.uk. (13)) (Fig S3B-F) we analysed early larval behaviour as a stratagem to probe the functional integrity of the late embryonic nervous system. Europe PMC Funders GroupMost behaviours in early larva were unaffected by the miRNA mutation ( Fig. S1, movie S1 and S2) except self-righting (SR) behaviour ( Fig. 1A-C, movies S3-S4): miRNA mutant larvae were unable to return to their normal orientation at the same speed as their wild type counterparts.By means of selective target ...

The regulated head-to-tail expression of Hox genes provides a coordinate system for the activation of specific programmes of cell differentiation according to axial level. Recent work indicates that Hox expression can be regulated via RNA processing but the underlying mechanisms and biological significance of this form of regulation remain poorly understood. Here we explore these issues within the developing Drosophila central nervous system (CNS). We show that the pan-neural RNA-binding protein (RBP) ELAV (Hu antigen) regulates the RNA processing patterns of the Hox gene Ultrabithorax (Ubx) within the embryonic CNS. Using a combination of biochemical, genetic and imaging approaches we demonstrate that ELAV binds to discrete elements within Ubx RNAs and that its genetic removal reduces Ubx protein expression in the CNS leading to the respecification of cellular subroutines under Ubx control, thus defining for the first time a specific cellular role of ELAV within the developing CNS. Artificial provision of ELAV in glial cells (a cell type that lacks ELAV) promotes Ubx expression, suggesting that ELAV-dependent regulation might contribute to cell type-specific Hox expression patterns within the CNS. Finally, we note that expression of abdominal A and Abdominal B is reduced in elav mutant embryos, whereas other Hox genes (Antennapedia) are not affected. Based on these results and the evolutionary conservation of ELAV and Hox genes we propose that the modulation of Hox RNA processing by ELAV serves to adapt the morphogenesis of the CNS to axial level by regulating Hox expression and consequently activating local programmes of neural differentiation.

Picao-Osorio et al. reveal pervasive effects of microRNA regulation on complex locomotor behaviors in Drosophila larvae: over 40% of microRNAs display...

There is increasing evidence regarding the role of chromosomal inversions in relevant biological processes such as local adaptation and speciation. A classic example of the adaptive role of chromosomal polymorphisms is given by the clines of inversion frequencies in Drosophila subobscura, repeatable across continents. Nevertheless, not much is known about the molecular variation associated with these polymorphisms. We characterized the genetic content of ca. 600 individuals from nine European populations following a latitudinal gradient by analysing 19 microsatellite loci from two autosomes (J and U) and the sex chromosome (A), taking into account their chromosomal inversions. Our results clearly demonstrate the molecular genetic uniformity within a given chromosomal inversion across a large latitudinal gradient, particularly from Groningen (Netherlands) in the north to Málaga (Spain) in the south, experiencing highly diverse environmental conditions. This low genetic differentiation within the same gene arrangement across the nine European populations is consistent with the local adaptation hypothesis for th evolutionof chromosomal polymorphisms. We also show the effective role of chromosomal inversions in maintaining different genetic pools within these inverted genomic regions even in the presence of high gene flow. Inversions represent thus an important barrier to gene flux and can help maintain specific allelic combinations with positive effects on fitness. Consistent patterns of microsatellite allele-inversion linkage disequilibrium particularly in loci within inversions were also observed. Finally, we identified areas within inversions presenting clinal variation that might be under selection.