Highlights d Drosophila DN1p clock neurons innervate the anterior optic tubercle (AOTU) d A subset of tubercular-bulbar (TuBu) neurons in the AOTU is inhibited by DN1p neurons d These TuBu neurons promote consolidated sleep during the day d Ellipsoid body ring neurons are downstream of sleepregulatory TuBu neurons

Riboflavin metabolites are critical components of the mitochondrial electron transport chain. Manole et al. describe the genetics, phenotypes and neuropathology of a large patient series with riboflavin-responsive neuropathy. Using in-vitro and in-vivo models, they reveal mitochondrial dysfunction in the disorder, and validate riboflavin esters as a potential therapeutic strategy.

Sleep is a highly conserved and essential behaviour in many species, including the fruit fly Drosophila melanogaster. In the wild, sensory signalling encoding environmental information must be integrated with sleep drive to ensure that sleep is not initiated during detrimental conditions. However, the molecular and circuit mechanisms by which sleep timing is modulated by the environment are unclear. Here we introduce a novel behavioural paradigm to study this issue. We show that in male fruit flies, onset of the daytime siesta is delayed by ambient temperatures above 29 °C. We term this effect Prolonged Morning Wakefulness (PMW). We show that signalling through the TrpA1 thermo-sensor is required for PMW, and that TrpA1 specifically impacts siesta onset, but not night sleep onset, in response to elevated temperatures. We identify two critical TrpA1-expressing circuits and show that both contact DN1p clock neurons, the output of which is also required for PMW. Finally, we identify the circadian blue-light photoreceptor CRYPTOCHROME as a molecular regulator of PMW, and propose a model in which the Drosophila nervous system integrates information encoding temperature, light, and time to dynamically control when sleep is initiated. Our results provide a platform to investigate how environmental inputs co-ordinately regulate sleep plasticity.

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Loss of FMR1 gene function results in fragile X syndrome (FXS), the most common heritable form of intellectual disability. The protein encoded from this locus (FMRP) is an RNA binding protein thought to primarily act as a translational regulator, however recent studies implicate FMRP in other mechanisms of gene regulation. Here, we demonstrate that the Drosophila fragile X homolog (dFMR1) biochemically interacts with the A-to-I RNA editing enzyme, dADAR. We found that dAdar and dfmr1 mutant larvae exhibit distinct morphological neuromuscular junction (NMJ) defects. Epistasis experiments based on these phenotypic differences suggest that dAdar acts downstream of dfmr1 and that dFMR1 modulates dADAR activity. Furthermore, sequence analyses revealed that loss or overexpression of dFMR1 affects editing efficiency on certain dADAR targets with defined roles in synaptic transmission. These results link dFMR1 with the RNA editing pathway and suggest that proper NMJ synaptic architecture requires modulation of dADAR activity by dFMR1.