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The Journal of neuroscience : the official journal of the Society for Neuroscience···
Identifying Rnb as a New Controller of Fruit Fly Daily Rhythms
Updated
Abstract
A newly identified gene regulates the function of the small ventral lateral neurons (s-LNvs), which act as the master pacemaker for circadian rhythms.
- The gene, termed Rnb, acts downstream of the nuclear receptor UNF to influence the s-LNvs’ role in circadian regulation.
- Mutations and targeted knockdowns of Rnb disrupt locomotor rhythms in fruit flies.
- Loss-of-function of Rnb affects molecular rhythms and the accumulation of PDF, a key neuropeptide, in the s-LNvs.
- The findings suggest distinct regulatory pathways for the molecular clocks within different pacemaker neuron subtypes.
Simplified
Behavioral circadian rhythms are controlled by multioscillator networks comprising functionally different subgroups of clock neurons. Studies have demonstrated that molecular clocks in the fruit flyare regulated differently in clock neuron subclasses to support their specific functions (Lee et al., 2016; Top et al., 2016). The nuclear receptor() represents a regulatory node that provides the small ventral lateral neurons (s-LNvs) unique characteristics as the master pacemaker (Beuchle et al., 2012). We previously showed that UNF interacts with the s-LNv molecular clocks by regulating transcription of the core clock gene() (Jaumouillé et al., 2015). To gain more insight into the mechanisms by which UNF contributes to the functioning of the circadian master pacemaker, we identified UNF target genes using chromatin immunoprecipitation. Our data demonstrate that a previously uncharacterized gene, which we termed(), acts downstream of UNF to regulate the function of the s-LNvs as the master circadian pacemaker. Mutations and LNv-targeted adult-restricted knockdown ofimpair locomotor rhythms. RNB localizes to the nucleus, and its loss-of-function blunts the molecular rhythms and output rhythms of the s-LNvs, particularly the circadian rhythms in PDF accumulation and axonal arbor remodeling. These results establish a second pathway by which UNF interacts with the molecular clocks in the s-LNvs and highlight the mechanistic differences in the molecular clockwork within the pacemaker circuit.Circadian behavior is generated by a pacemaker circuit comprising diverse classes of pacemaker neurons, each of which contains a molecular clock. In addition to the anatomical and functional diversity, recent studies have shown the mechanistic differences in the molecular clockwork among the pacemaker neurons inHere, we identified the molecular characteristics distinguishing the s-LNvs, the master pacemaker of the locomotor rhythms, from other clock neuron subtypes. We demonstrated that a newly identified geneis an s-LNv-specific regulator of the molecular clock and essential for the generation of circadian locomotor behavior. Our results provide additional evidence to the emerging view that the differential regulation of the molecular clocks underlies the functional differences among the pacemaker neuron subgroups. Drosophila melanogaster unfulfilled unf period per CG7837R and B Rnb Rnb Drosophila Rnb SIGNIFICANCE STATEMENT
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