Central and peripheral clocks are coupled by a neuropeptide pathway in Drosophila

Mareike Selcho,Carola Millán,Gregor Bergmann,Lilian Ubillo,Valeria Silva,John Ewer,Christian Wegener,Angelina Palacios-Muñoz,Jiangtian Chen,Franziska Ruf,Chihiro Ito

doi:10.1038/ncomms15563

Abstract

Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour. Despite its importance for optimal performance and health, the mechanism of clock coordination is poorly understood. Here we dissect the pathway through which the circadian clock of Drosophila imposes daily rhythmicity to the pattern of adult emergence. Rhythmicity depends on the coupling between the brain clock and a peripheral clock in the prothoracic gland (PG), which produces the steroid hormone, ecdysone. Time information from the central clock is transmitted via the neuropeptide, sNPF, to non-clock neurons that produce the neuropeptide, PTTH. These secretory neurons then forward time information to the PG clock. We also show that the central clock exerts a dominant role on the peripheral clock. This use of two coupled clocks could serve as a paradigm to understand how daily steroid hormone rhythms are generated in animals.

Highlights

Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour
8 pairs of ventral lateral neurons’ (LNs) (LNvs) express the neuropeptide pigment dispersing factor (PDF), which is key for the expression of behavioural circadian rhythmicity[25,26], including rhythmic adult emergence[16,17], and is one of the intercellular signals that coordinates the phase of the various clock neurons[27,28]
Since the levels of ecdysone must fall below threshold levels in order for emergence to occur[30,31], this anatomical arrangement suggests that PDF, acting on prothoracicotropic hormone (PTTH) neurons, could provide a pathway through which the central clock could influence the prothoracic gland (PG) clock and gate the time of adult emergence

Summary

Introduction

Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour. We show that a similar anatomical relationship between the small ventral LNs (sLNvs), a critical subclass of central pacemaker neurons, and the PTTH neurons exists in the pharate adult brain of the fruit fly This connection is not effected by PDF but by short NPF (sNPF), a second neuropeptide produced by sLNv neurons[22]. Our results are reminiscent of the control of the circadian rhythm of glucocorticoid (GC) production in mammals, which depends on functional clocks in the SCN and in the adrenal gland In this case, the mechanisms through which central and peripheral clocks are coordinated to time steroid hormone action are still incompletely understood. The control of emergence in Drosophila may provide a genetically tractable model to uncover general mechanisms behind such daily endocrine rhythms

Methods

Results

Conclusion