Understanding the cellular and molecular bases of behavior is one of the principal goals of contemporary neuroscience research. The fruit fly Drosophila melanogaster has proven to be an excellent model system for genetic and molecular studies of behavior and the nervous system. Recent advances, including techniques for cell-specific expression and the completion of the fly genome project, have underscored the utility of Drosophila for this type of functional analysis. In our continuing studies, we take advantage of the Drosophila system to better understand the circadian regulation of a behavior known as eclosion (the emergence or ecdysis of the Drosophila adult). The circadian regulation of this behavior is well understood in formal terms, and experimental studies have identified candidate cell types and gene products that are important modulatory elements of the clock output pathway controlling eclosion. Our previous studies identified a gene called lark, which encodes an RNA-binding protein that functions in the clock control of eclosion. Recent studies have documented circadian oscillations in LARK abundance, and shown that the protein is localized within peptidergic neurons (CCAP cells) that are essential for the physiological regulation of ecdysis (adult eclosion being the final ecdysis in the Drosophila life cycle). The CCAP cells contain a neuropeptide called Crustacean Cardioactive Peptide (CCAP), and CCAP release from these neurons drives ecdysis behavior. LARK exhibits a dramatic circadian oscillation in abundance within the CCAP neurons, and we hypothesize that the clock regulation of LARK within these peptidergic neurons is important for circadian control of eclosion. This continuation application is focused on the analysis of LARK within the CCAP neurons. The goals of the work are to: 1) analyze the regulation of LARK within the CCAP cell population, 2) ascertain whether the CCAP cells and CCAP neuropeptide are essential for the clock control of eclosion, 3) determine if LARK function within the CCAP cells is essential for rhythmicity, and 4) define the target mRNAs of LARK within the CCAP cell population. Such an analysis will provide significant information about the cellular and molecular signaling pathways governing the clock regulation of a specific behavior and contribute to a general framework for understanding the circadian control of behavior in mammalian and non-mammalian species.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MDCN-6 (01))
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Twery, Michael
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Tufts University
Schools of Medicine
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Jackson, F Rob; Ng, Fanny S; Sengupta, Sukanya et al. (2015) Glial cell regulation of rhythmic behavior. Methods Enzymol 552:45-73
Huang, Yanmei; McNeil, Gerard P; Jackson, F Rob (2014) Translational regulation of the DOUBLETIME/CKI?/? kinase by LARK contributes to circadian period modulation. PLoS Genet 10:e1004536
Chen, Audrey; Ng, Fanny; Lebestky, Tim et al. (2013) Dispensable, redundant, complementary, and cooperative roles of dopamine, octopamine, and serotonin in Drosophila melanogaster. Genetics 193:159-76
Huang, Yanmei; Ainsley, Joshua A; Reijmers, Leon G et al. (2013) Translational profiling of clock cells reveals circadianly synchronized protein synthesis. PLoS Biol 11:e1001703
Sundram, Vasudha; Ng, Fanny S; Roberts, Mary A et al. (2012) Cellular requirements for LARK in the Drosophila circadian system. J Biol Rhythms 27:183-95
Tangredi, Michelle M; Ng, Fanny S; Jackson, F Rob (2012) The C-terminal kinase and ERK-binding domains of Drosophila S6KII (RSK) are required for phosphorylation of the protein and modulation of circadian behavior. J Biol Chem 287:16748-58
Ng, Fanny S; Tangredi, Michelle M; Jackson, F Rob (2011) Glial cells physiologically modulate clock neurons and circadian behavior in a calcium-dependent manner. Curr Biol 21:625-34
Jackson, F Rob (2011) Glial cell modulation of circadian rhythms. Glia 59:1341-50
Huang, Yanmei; Howlett, Eric; Stern, Michael et al. (2009) Altered LARK expression perturbs development and physiology of the Drosophila PDF clock neurons. Mol Cell Neurosci 41:196-205
Draper, Isabelle; Tabaka, Meg E; Jackson, F Rob et al. (2009) The evolutionarily conserved RNA binding protein SMOOTH is essential for maintaining normal muscle function. Fly (Austin) 3:235-46

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