PDF Signaling Is an Integral Part of the Drosophila Circadian Molecular Oscillator
| Autor: | Bart Deplancke, Shaul Mezan, Sebastian Kadener, Jean Daniel Feuz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transcription Genetic Circadian clock Regulator CLOCK Proteins Biology Bioinformatics RAR-related orphan receptor alpha Models Biological General Biochemistry Genetics and Molecular Biology Fluorescence Article 03 medical and health sciences Biological Clocks Genes Reporter Animals Drosophila Proteins Circadian rhythm Transcription factor lcsh:QH301-705.5 Neurons Neuropeptides fungi transcriptional fluorescent reporters Bacterial circadian rhythms Circadian Rhythm 030104 developmental biology Drosophila melanogaster circadian nervous system lcsh:Biology (General) brain culture Drosophila Nerve Net Neuroscience CLK Drosophila Protein Signal Transduction |
| Zdroj: | Cell Reports, Vol 17, Iss 3, Pp 708-719 (2016) Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | Summary Circadian clocks generate 24-hr rhythms in physiology and behavior. Despite numerous studies, it is still uncertain how circadian rhythms emerge from their molecular and neural constituents. Here, we demonstrate a tight connection between the molecular and neuronal circadian networks. Using fluorescent transcriptional reporters in a Drosophila ex vivo brain culture system, we identified a reciprocal negative regulation between the master circadian regulator CLK and expression of pdf, the main circadian neuropeptide. We show that PDF feedback is required for maintaining normal oscillation pattern in CLK-driven transcription. Interestingly, we found that CLK and neuronal firing suppresses pdf transcription, likely through a common pathway involving the transcription factors DHR38 and SR, establishing a direct link between electric activity and the circadian system. In sum, our work provides evidence for the existence of an uncharacterized CLK-PDF feedback loop that tightly wraps together the molecular oscillator with the circadian neuronal network in Drosophila. Graphical Abstract Highlights • Monitoring circadian transcription ex vivo using fluorescent reporters • CLK activation in the LNvs provokes downregulation in CLK activity in LNds and DNs • Reciprocal negative regulation of CLK activity and pdf transcription and signaling • PDF signaling is required for the normal oscillation pattern in CLK activity Using fluorescence transcriptional reporters in an ex vivo brain culture, Mezan et al. describe the existence of a reciprocal negative regulation between CLK activity and pdf transcription and signaling. Hence, this work uncovers an uncharacterized regulatory loop in Drosophila pacemaker neurons that integrates essential intra and extracellular circadian factors. |
| Databáze: | OpenAIRE |
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