Use this URL to cite or link to this record in EThOS:
Title: The small GTPase Rho1 couples peptidergic control of circadian behaviour to molecular oscillator function in Drosophila melanogaster
Author: Ramirez Moreno, Miguel
ISNI:       0000 0004 6500 7895
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
The fruit fly Drosophila melanogaster constitutes a resourceful and representative model organism for investigation of the circadian clock mechanisms that control daily rhythms. Circadian control of sleep/wake rhythms in both flies and mammals requires not only molecular oscillators inside the clock cells, but also intercellular communication circuits. How these oscillators couple to relevant patterns of signals like neuropeptides or neuronal firing remains, to a large extent, unclear. This project presents evidences that the small GTPase Rho1 (homologue of the mammalian RhoA), a regulator of actin dynamics, controls circadian locomotor behaviour in a dosage-dependent manner. Flies with specific reduction of Rho1 levels inside their adult pacemaker neurons [the ventral lateral neurons (LNvs) that express the neuropeptide Pigment Dispersing Factor (PDF)] effectively lose their capacity of sustaining rhythms in free run devoid of external stimuli. When environmental cues are present, these flies exhibit a heightened sensitivity and their activity rhythms are more dependent of environmental cycles. Remarkable, this happens in the context of normal molecular oscillators across the clock circuitry in the brain. This discoordination between clocks and behaviour points to a disruption at the circuit level that weakens the output response. Diverse experiments have implicated an abnormality in signalling from the small LNv (s-LNv) dorsal axons as the cause of this phenotype: 1) the clock-controlled rhythms of remodelling of the s-LNv dorsal axons are abrogated upon Rho1 knockdown; 2) The Rho1 deficit behavioural phenotype is rescued by manipulations that shift pacemaker function from the s-LNvs to other clock neurons and 3) the Rho1 knockdown phenotypes in free run and under light cycles are hypostatic to the removal of the PDF Receptor (Pdfr) gene. These observations suggest that neuronal activity rhythms in PDFR clock neurons and dependent output circuits may also be disrupted. Summarising the results, the Rho1 activity couples the cellular oscillators to the circadian locomotor behaviour by regulating peptidergic s-LNv signalling. Thus, the characterization of the phenotype caused by the depletion of Rho1 has uncovered a disruption of the clock function at the circuit level without a strong impact on cellular oscillator function.
Supervisor: Wijnen, Herman Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available