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Diversification of molecular clockwork for tissue specific function: insight from novel Drosophila Clock mutant homologous to mouse Clock allele
Eunjoo Cho1,2, Eunjoo Cho1,2, Euna Lee2,3, Euna Lee2,3, Eun Young Kim1,2,3,*,#, Eun Young Kim1,2,3,*,#
1Department of Brain Science and 1Department of Brain Science and 2Chronic Inflammatory Disease Research Center and 2Chronic Inflammatory Disease Research Center and 3BK21 Plus program, Neuroscience Graduate program and 3BK21 Plus program, Neuroscience Graduate program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 16499, Republic of Korea
Abstract
The circadian clock system enables organisms to anticipate the rhythmic environmental changes and to manifest behavior and physiology at advantageous times of day. Transcriptional/translational feedback loop (TTFL) is the basic feature of eukaryotic circadian clock and is based on the rhythmic association of circadian transcriptional activator and repressor. In Drosophila, repression of dCLOCK/CYCLE (dCLK/CYC) mediated transcription by PERIOD (PER) is critical for inducing circadian rhythms of gene expression. Pacemaker neurons in the brain control specific circadian behaviors upon environmental timing cues such as light and temperature cycle. We show here that amino acids 657-707 of dCLK is important for the transcriptional activation and the association with PER both in vitro and in vivo. Flies expressing dCLK lacking AA657-707 in Clkout genetic background, homologous to the mouse Clock allele where exon 19 region is deleted, display pacemaker-neuron-dependent perturbation of the molecular clockwork. Namely, the molecular rhythms in light-cycle-sensitive pacemaker neurons such as ventral lateral neurons (LNvs) were significantly disrupted but those in temperature-cycle-sensitive pacemaker neurons such as dorsal neurons (DNs) were robust. Our results suggest that the dCLK-controlled TTFL diversified in pacemaker-neuron-dependent manner which contribute to specific functions such as different sensitivities to entraining cues.
Abstract, Accepted Manuscript(in press) [Submitted on October 17, 2016, Accepted on October 18, 2016]
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