Project

Back to overview

Molecular genetics of behavior: role of a putative regulator of the Wnt/Wingless signaling pathway in the generation of circadian behavioral rhythms

English title Molecular genetics of behavior: role of a putative regulator of the Wnt/Wingless signaling pathway in the generation of circadian behavioral rhythms
Applicant Nagoshi Emi
Number 169548
Funding scheme Project funding (Div. I-III)
Research institution Département de Génétique et Evolution Faculté des Sciences Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Genetics
Start/End 01.04.2017 - 31.03.2020
Approved amount 429'000.00
Show all

All Disciplines (4)

Discipline
Genetics
Molecular Biology
Cellular Biology, Cytology
Neurophysiology and Brain Research

Keywords (8)

Circadian rhythms; Genetic screens; Drosophila; Genetics; Genome editing; Behavior; Neural circuits; Wnt/wingless signaling pathway

Lay Summary (French)

Lead
Comment le cerveau contrôle le comportement est une question centrale dans la neurobiologie. Pour adresser cette question, nous utilisons la Drosophile melanogaster comme un modèle et étudions le mécanisme de rythme circadien. Le rythme circadien contrôle les activités quotidiennes dans la plupart des organismes, en particulier les cycles veille-sommeil. Nous étudierons le mécanisme par lequel CG783, qui est un gène précédemment inconnu, contrôle le rythme circadien.
Lay summary

Contenu et objectifs du travail de recherche

CG7837 a proposé d’agir dans la voie Wnt/Wingless, de signalisation qui contrôlent les processus physiologiques normaux et est déréglementé dans de nombreuses maladies tell que les cancers. Nous émettons l’hypothèse que la CG7837 relie la voie de signalisation Wnt/Wingless et le mécanisme de l’horloge moléculaire pour contrôler le rythme circadien. Nous étudierons cette hypothèse en effectuant les dépistage génétiques pour identifier les facteurs qui interagissent fonctionnellement avec CG7837.

 

Contexte scientifique et social du projet de recherche

Le résultat de cette recherche donnera des avancées significatives dans la biologie circadienne et peut également faire la lumière sur un nouveau rôle de la voie de signalisation Wnt/Wingless. Les mutations dans le gène ARMC5, qui est l'homologue de mammifère de CG7837, sont liées à l'hyperplasie surrénalienne macronodulaire. Donc, les nouvelles connaissances acquises sur la fonction et le mécanisme d'action de CG7837 devraient également fournir des informations importantes pour comprendre les mécanismes de la tumorigenèse l'ARMC5-dépendante.

 

Direct link to Lay Summary Last update: 03.04.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Decoding Drosophila circadian pacemaker circuit
(2019), Decoding Drosophila circadian pacemaker circuit, in Current Opinion in Insect Science, 33.
Nitric Oxide Mediates Neuro-Glial Interaction that Shapes Drosophila Circadian Behavior
Nagoshi Emi, Kozlov Anatoly (2019), Nitric Oxide Mediates Neuro-Glial Interaction that Shapes Drosophila Circadian Behavior, in bioRxiv, 700971.
Drosophila Models of Sporadic Parkinson’s Disease
Nagoshi Emi (2018), Drosophila Models of Sporadic Parkinson’s Disease, in International Journal of Molecular Sciences, 3343.
Parallel roles of transcription factors dFOXO and FER2 in the development and maintenance of dopaminergic neurons.
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, e1007271.
Single-cell Resolution Fluorescence Live Imaging of Drosophila Circadian Clocks in Larval Brain Culture.
Sabado V Nagoshi E. (2018), Single-cell Resolution Fluorescence Live Imaging of Drosophila Circadian Clocks in Larval Brain Culture., in J Vis Exp, 131.
Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture.
Sabado V Vienne L Nagoshi E. (2017), Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture., in Front Cell Neurosci, 317.
A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms.
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.
Guidelines for Genome-Scale Analysis of Biological Rhythms
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, 380.
Transforming Growth Factor β/Activin signaling in neurons increases susceptibility to starvation
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, e0187054.
Fluorescence live imaging of Drosophila circadian pacemaker neurons
SabadoVirginie, NagoshiEmi, Fluorescence live imaging of Drosophila circadian pacemaker neurons, Springer Nature Switzerland AG, Switzerland.

Collaboration

Group / person Country
Types of collaboration
Michael Rosbash's lab/Brandeis University United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Associated projects

Number Title Start Funding scheme
130387 Genetic control of neuronal diversity: role of Fer2, a cell-type specific transcription factor essential for the development of the circadian circuit 01.09.2010 Project funding (Div. I-III)
149893 Molecular and neural mechanisms of circadian locomotor behavior 01.11.2013 Project funding (Div. I-III)

Abstract

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.
-