Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 28, Pages 6673-6685Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3286-16.2017
Keywords
behavior; chromatin immunoprecipitation; circadian rhythms; Drosophila; molecular mechanism; pacemaker neurons
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Funding
- JST PRESTO program, Swiss National Science Foundation [31003A_149893]
- European Research Council [ERC-StG- 311194]
- Georges & Antoine Claraz Donation
- University of Geneva
- Bloomington Drosophila Stock Center [NIH P40OD018537]
- Swiss National Science Foundation (SNF) [31003A_149893] Funding Source: Swiss National Science Foundation (SNF)
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Behavioral circadian rhythms are controlled by multioscillator networks comprising functionally different subgroups of clock neurons. Studies have demonstrated that molecular clocks in the fruit fly Drosophila melanogaster are regulated differently in clock neuron subclasses to support their specific functions (Lee et al., 2016; Top et al., 2016). The nuclear receptor unfulfilled (unf) represents a regulatory node that provides the small ventral lateral neurons (s-LNvs) unique characteristics as the master pacemaker (Beuchle et al., 2012). Wepreviously showed that UNF interacts with the s-LNv molecular clocks by regulating transcription of the core clock gene period (per) (Jaumouille ' 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 CG7837, which we termed R and B (Rnb), acts downstream of UNF to regulate the function of the s-LNvs as the master circadian pacemaker. Mutations and LNv-targeted adult-restricted knockdown of Rnb impair 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.
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