A Screening of UNF Targets Identifies <i>Rnb</i>, a Novel Regulator of <i>Drosophila</i> Circadian Rhythms

Kozlov, Anatoly; Jaumouillé, Edouard; Almeida, Pedro Machado; Koch, Rafael; Rodriguez, Joseph; Abruzzi, Katharine C.; Nagoshi, Emi

doi:10.1523/jneurosci.3286-16.2017

Cited by 8 publications

(8 citation statements)

References 43 publications

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“…For quantification of CCHa1 staining, the polygon selection tool of Fiji was used to select each cell body of the DN 1a neurons. For quantification of PDF staining and area of branching at the s-LN v terminals, the polygon selection tool was used to select the area of the branching s-LN v dorsal terminals that were visualized upon Z-projection of multiple confocal stacks ( Kozlov et al, 2017 ). To visualize projections of the DN 1a , s-LN v , and l-LN v neurons, we traced and reconstituted their projections using the Fiji plugin Simple Neurite Tracer ( Longair et al, 2011 ).…”

Section: Methodsmentioning

confidence: 99%

The CCHamide1 Neuropeptide Expressed in the Anterior Dorsal Neuron 1 Conveys a Circadian Signal to the Ventral Lateral Neurons in Drosophila melanogaster

et al. 2018

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The fruit fly Drosophila melanogaster possesses approximately 150 brain clock neurons that control circadian behavioral rhythms. Even though individual clock neurons have self-sustaining oscillators, they interact and synchronize with each other through a network. However, little is known regarding the factors responsible for these network interactions. In this study, we investigated the role of CCHamide1 (CCHa1), a neuropeptide expressed in the anterior dorsal neuron 1 (DN1a), in intercellular communication of the clock neurons. We observed that CCHa1 connects the DN1a clock neurons to the ventral lateral clock neurons (LNv) via the CCHa1 receptor, which is a homolog of the gastrin-releasing peptide receptor playing a role in circadian intercellular communications in mammals. CCHa1 knockout or knockdown flies have a generally low activity level with a special reduction of morning activity. In addition, they exhibit advanced morning activity under light-dark cycles and delayed activity under constant dark conditions, which correlates with an advance/delay of PAR domain Protein 1 (PDP1) oscillations in the small-LNv (s-LNv) neurons that control morning activity. The terminals of the s-LNv neurons show rather high levels of Pigment-dispersing factor (PDF) in the evening, when PDF is low in control flies, suggesting that the knockdown of CCHa1 leads to increased PDF release; PDF signals the other clock neurons and evidently increases the amplitude of their PDP1 cycling. A previous study showed that high-amplitude PDP1 cycling increases the siesta of the flies, and indeed, CCHa1 knockout or knockdown flies exhibit a longer siesta than control flies. The DN1a neurons are known to be receptive to PDF signaling from the s-LNv neurons; thus, our results suggest that the DN1a and s-LNv clock neurons are reciprocally coupled via the neuropeptides CCHa1 and PDF, and this interaction fine-tunes the timing of activity and sleep.

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Section: Methodsmentioning

confidence: 99%

The CCHamide1 Neuropeptide Expressed in the Anterior Dorsal Neuron 1 Conveys a Circadian Signal to the Ventral Lateral Neurons in Drosophila melanogaster

et al. 2018

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“…Of note, no statistical difference in axonal areas was detected between ZT2 and ZT14 both in the mutants and the control genotype ( Fig 3C). Thus, this quantification method was probably not sensitive enough to detect daily structural changes in this genetic background, although the same method successfully detected rhythmic changes in axonal structure in our previous study [40]. Nevertheless, these observations suggest that NOS deficiency leads to defects in the morphology of s-LNvs dorsal projections and disturbances in the rhythms of PDF accumulation.…”

Section: Nos Is a Regulator Of Morphogenesis Of The S-lnv Axonsmentioning

confidence: 68%

“…The anti-PER signal was quantified as previously described [14]. Axonal branching patterns of s-LNvs and PDF levels were quantified as previously described [40].…”

Section: Immunocytochemistry Microscopy and Quantificationmentioning

confidence: 99%

Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior

2020

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Drosophila circadian behavior relies on the network of heterogeneous groups of clock neurons. Short-and long-range signaling within the pacemaker circuit coordinates molecular and neural rhythms of clock neurons to generate coherent behavioral output. The neurochemistry of circadian behavior is complex and remains incompletely understood. Here we demonstrate that the gaseous messenger nitric oxide (NO) is a signaling molecule linking circadian pacemaker to rhythmic locomotor activity. We show that mutants lacking nitric oxide synthase (NOS) have behavioral arrhythmia in constant darkness, although molecular clocks in the main pacemaker neurons are unaffected. Behavioral phenotypes of mutants are due in part to the malformation of neurites of the main pacemaker neurons, s-LNvs. Using cell-type selective and stage-specific gain-and loss-of-function of NOS, we also demonstrate that NO secreted from diverse cellular clusters affect behavioral rhythms. Furthermore, we identify the perineurial glia, one of the two glial subtypes that form the blood-brain barrier, as the major source of NO that regulates circadian locomotor output. These results reveal for the first time the critical role of NO signaling in the Drosophila circadian system and highlight the importance of neuro-glial interaction in the neural circuit output.

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“…The mean pixel value of each cell in a given subgroup was calculated by subtracting the mean pixel value of the background and plotted as relative intensity normalized to the value of the control group at CT0. PDF levels in the s-LNv dorsal terminals were measured as described in Kozlov et al (2017) . Briefly, the region of interest (ROI) for the axonal termini (from the tip of the s-LNv dorsal termini until where the terminal arbors first branch) was specified manually with the polygon selection tool in Fiji and the intensity sum within each ROI was measured.…”

Section: Methodsmentioning

confidence: 99%

Uncovering the Roles of Clocks and Neural Transmission in the Resilience of Drosophila Circadian Network

2021

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Studies of circadian locomotor rhythms in Drosophila melanogaster gave evidence to the preceding theoretical predictions on circadian rhythms. The molecular oscillator in flies, as in virtually all organisms, operates using transcriptional-translational feedback loops together with intricate post-transcriptional processes. Approximately150 pacemaker neurons, each equipped with a molecular oscillator, form a circuit that functions as the central pacemaker for locomotor rhythms. Input and output pathways to and from the pacemaker circuit are dissected to the level of individual neurons. Pacemaker neurons consist of functionally diverse subclasses, including those designated as the Morning/Master (M)-oscillator essential for driving free-running locomotor rhythms in constant darkness and the Evening (E)-oscillator that drives evening activity. However, accumulating evidence challenges this dual-oscillator model for the circadian circuit organization and propose the view that multiple oscillators are coordinated through network interactions. Here we attempt to provide further evidence to the revised model of the circadian network. We demonstrate that the disruption of molecular clocks or neural output of the M-oscillator during adulthood dampens free-running behavior surprisingly slowly, whereas the disruption of both functions results in an immediate arrhythmia. Therefore, clocks and neural communication of the M-oscillator act additively to sustain rhythmic locomotor output. This phenomenon also suggests that M-oscillator can be a pacemaker or a downstream path that passively receives rhythmic inputs from another pacemaker and convey output signals. Our results support the distributed network model and highlight the remarkable resilience of the Drosophila circadian pacemaker circuit, which can alter its topology to maintain locomotor rhythms.

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A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms

Cited by 8 publications

References 43 publications

The CCHamide1 Neuropeptide Expressed in the Anterior Dorsal Neuron 1 Conveys a Circadian Signal to the Ventral Lateral Neurons in Drosophila melanogaster

The CCHamide1 Neuropeptide Expressed in the Anterior Dorsal Neuron 1 Conveys a Circadian Signal to the Ventral Lateral Neurons in Drosophila melanogaster

Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior

Uncovering the Roles of Clocks and Neural Transmission in the Resilience of Drosophila Circadian Network

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