Circadian rhythms; Genetic screens; Drosophila; Genetics; Genome editing; Behavior; Neural circuits; Wnt/wingless signaling pathway
(2019), Decoding Drosophila circadian pacemaker circuit, in Current Opinion in Insect Science
Nagoshi Emi, Kozlov Anatoly (2019), Nitric Oxide Mediates Neuro-Glial Interaction that Shapes Drosophila Circadian Behavior, in bioRxiv
Nagoshi Emi (2018), Drosophila Models of Sporadic Parkinson’s Disease, in International Journal of Molecular Sciences
Tas D Stickley L Miozzo F Koch R Loncle N Sabado V Gnägi B Nagoshi E. (2018), Parallel roles of transcription factors dFOXO and FER2 in the development and maintenance of dopaminergic neurons., in PLOS Genetics
Sabado V Nagoshi E. (2018), Single-cell Resolution Fluorescence Live Imaging of Drosophila Circadian Clocks in Larval Brain Culture., in J Vis Exp
Sabado V Vienne L Nagoshi E. (2017), Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture., in Front Cell Neurosci
Kozlov A Jaumouillé E Machado Almeida P Koch R Rodriguez J Abruzzi KC Nagoshi E. (2017), A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms., in Journal of Neuroscience
, 37(28), 6673-6685.
Hughes ME1 Abruzzi KC2 Allada R3 Anafi R4 Arpat AB56 Asher G7 Baldi P8 de Bekker C9 Bell-Pe (2017), Guidelines for Genome-Scale Analysis of Biological Rhythms, in J Biol Rhythms
Chng WA Koch R Li X Kondo S Nagoshi E Lemaitre B (2017), Transforming Growth Factor β/Activin signaling in neurons increases susceptibility to starvation, in PLOS One
SabadoVirginie, NagoshiEmi, Fluorescence live imaging of Drosophila circadian pacemaker neurons
, Springer Nature Switzerland AG, Switzerland.
How the brain generates behavior is a central question in neurobiology. To address this question, we have been focusing on the circadian (near 24-hr cycle) locomotor behavior, the highly robust, quantifiable and universal behavior, as a paradigm in the genetically tractable model organism, Drosophila melanogaster. Circadian behavioral rhythms are controlled by the neural circuit composed of multiple subtypes of pacemaker neurons, each of which contains a molecular clock that generates molecular rhythms through transcriptional feedback loops. Despite the advances in understanding the molecular clock feedback loops and the circadian neural circuit organization, a large gap remains in our understanding of how the molecular clockwork leads to the coherent rhythmic behavior. In this proposal, to better understand the mechanistic link between the molecular clockwork and behavioral output, we will investigate the role of the CG7837 gene, a newly identified gene critical for the generation of circadian locomotor behavior. CG7837 is a putative regulator of the Wnt/Wingless signaling pathway and a target of the nuclear receptor UNF (DHR51), which is required for the molecular rhythms and normal output of the master pacemaker neurons (the M-oscillator) of the circadian circuit. Taken together with the notion that several members of the Wnt/Wingless signaling pathway participate in the molecular clock feedback loops, our results postulate the hypothesis that CG7837 acts at the interface between the circadian molecular clock and the Wnt/Wingless signaling pathway in the functioning of the M-oscillator, thereby controlling the circadian behavior. We will therefore take a combination of targeted and non-biased molecular genetic approaches to systematically explore the role of CG7837 and the Wnt/Wingless signaling pathway in the M-oscillator and their interaction. Specifically, we will: (1) characterize CG7837 spatial and temporal expression patterns; (2) investigate genetic interactions between CG7837, molecular clock components and Wnt/Wingless signaling pathway components in the generation of locomotor rhythms; and (3) identify dominant modifiers of CG7837 loss-of-function by genetic screens. The outcome of this research will yield significant advances in the circadian biology and may also shed light on a novel role of the Wnt/Wingless signaling pathway. Mutations in the ARMC5 gene, the mammalian homolog of CG7837, are linked to the corticotropin-independent macronodular adrenal hyperplasia. Therefore, the newly gained knowledge on the function and mechanism of action of CG7837 should also provide important information to understand the mechanism of ARMC5-dependent tumorigenesis.