Mating disrupts morning anticipation in Drosophila melanogaster females.

After mating, the physiology of Drosophila females undergo several important changes, some of which are reflected in their rest-activity cycles. To explore the hypothesis that mating modifies the temporal organization of locomotor activity patterns, we recorded fly activity by a video tracking method. Monitoring rest-activity patterns under light/dark (LD) cycles indicated that mated females lose their ability to anticipate the night-day transition, in stark contrast to males and virgins. This postmating response is mediated by the activation of the sex peptide receptor (SPR) mainly on pickpocket (ppk) expressing neurons, since reducing expression of this receptor in these neurons restores the ability to anticipate the LD transition in mated females. Furthermore, we provide evidence of connectivity between ppk+ neurons and the pigment-dispersing factor (PDF)-positive ventral lateral neurons (sLNv), which play a central role in the temporal organization of daily activity. Since PDF has been associated to the generation of the morning activity peak, we hypothesized that the mating signal could modulate PDF levels. Indeed, we confirm that mated females have reduced PDF levels at the dorsal protocerebrum; moreover, SPR downregulation in ppk+ neurons mimics PDF levels observed in males. In sum, our results are consistent with a model whereby mating-triggered signals reach clock neurons in the fly central nervous system to modulate the temporal organization of circadian behavior according to the needs of the new status.

Investigating local and systemic intestinal signalling in health and disease with Drosophila.

Whole-body health relies on complex inter-organ signalling networks that enable organisms to adapt to environmental perturbations and to changes in tissue homeostasis. The intestine plays a major role as a signalling centre by producing local and systemic signals that are relayed to the body and that maintain intestinal and organismal homeostasis. Consequently, disruption of intestinal homeostasis and signalling are associated with systemic diseases and multi-organ dysfunction. In recent years, the fruit fly Drosophila melanogaster has emerged as a prime model organism to study tissue-intrinsic and systemic signalling networks of the adult intestine due to its genetic tractability and functional conservation with mammals. In this Review, we highlight Drosophila research that has contributed to our understanding of how the adult intestine interacts with its microenvironment and with distant organs. We discuss the implications of these findings for understanding intestinal and whole-body pathophysiology, and how future Drosophila studies might advance our knowledge of the complex interplay between the intestine and the rest of the body in health and disease.

Decapentaplegic Acutely Defines the Connectivity of Central Pacemaker Neurons in Drosophila.

Rhythmic rest-activity cycles are controlled by an endogenous clock. In Drosophila, this clock resides in ∼150 neurons organized in clusters whose hierarchy changes in response to environmental conditions. The concerted activity of the circadian network is necessary for the adaptive responses to synchronizing environmental stimuli. Thus far, work was devoted to unravel the logic of the coordination of different clusters focusing on neurotransmitters and neuropeptides. We further explored communication in the adult male brain through ligands belonging to the bone morphogenetic protein (BMP) pathway. Herein we show that the lateral ventral neurons (LNvs) express the small morphogen decapentaplegic (DPP). DPP expression in the large LNvs triggered a period lengthening phenotype, the downregulation of which caused reduced rhythmicity and affected anticipation at dawn and dusk, underscoring DPP per se conveys time-of-day relevant information. Surprisingly, DPP expression in the large LNvs impaired circadian remodeling of the small LNv axonal terminals, likely through local modulation of the guanine nucleotide exchange factor Trio. These findings open the provocative possibility that the BMP pathway is recruited to strengthen/reduce the connectivity among specific clusters along the day and thus modulate the contribution of the clusters to the circadian network.SIGNIFICANCE STATEMENT The circadian clock relies on the communication between groups of so-called clock neurons to coordinate physiology and behavior to the optimal times across the day, predicting and adapting to a changing environment. The circadian network relies on neurotransmitters and neuropeptides to fine-tune connectivity among clock neurons and thus give rise to a coherent output. Herein we show that decapentaplegic, a ligand belonging to the BMP retrograde signaling pathway required for coordinated growth during development, is recruited by a group of circadian neurons in the adult brain to trigger structural remodeling of terminals on a daily basis.

Rhythmic Behavior Is Controlled by the SRm160 Splicing Factor in Drosophila melanogaster.

Circadian clocks organize the metabolism, physiology, and behavior of organisms throughout the day-night cycle by controlling daily rhythms in gene expression at the transcriptional and post-transcriptional levels. While many transcription factors underlying circadian oscillations are known, the splicing factors that modulate these rhythms remain largely unexplored. A genome-wide assessment of the alterations of gene expression in a null mutant of the alternative splicing regulator SR-related matrix protein of 160 kDa (SRm160) revealed the extent to which alternative splicing impacts on behavior-related genes. We show that SRm160 affects gene expression in pacemaker neurons of the Drosophila brain to ensure proper oscillations of the molecular clock. A reduced level of SRm160 in adult pacemaker neurons impairs circadian rhythms in locomotor behavior, and this phenotype is caused, at least in part, by a marked reduction in period (per) levels. Moreover, rhythmic accumulation of the neuropeptide PIGMENT DISPERSING FACTOR in the dorsal projections of these neurons is abolished after SRm160 depletion. The lack of rhythmicity in SRm160-downregulated flies is reversed by a fully spliced per construct, but not by an extra copy of the endogenous locus, showing that SRm160 positively regulates per levels in a splicing-dependent manner. Our findings highlight the significant effect of alternative splicing on the nervous system and particularly on brain function in an in vivo model.