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Developmental requirements and network properties of the Drosophila circadian clock circuit

Developmental requirements and network properties of the Drosophila circadian clock circuit
Developmental requirements and network properties of the Drosophila circadian clock circuit
CLOCK/CYCLE (CLK/CYC) and PERIOD/TIMELESS (PER/TIM) are heterodimers which cyclically inhibit one another transcriptionally and post-translationally, required in adult Drosophila for the molecular oscillation controlling daily rhythms in activity. Prior work in the lab established that developmental reduction of PER and subsequent adult reintroduction does not affect adult rhythmic behaviour, whilst developmental PER overexpression or CYC reduction does. I sought to characterise the developmental role of CYC. Developmental CYC reduction specific to metamorphosis can impact adult behavioural rhythms, but CYC restriction throughout development does not appear to disrupt adult molecular rhythms. Developmental CYC restriction results aberrant neuroanatomy of small lateral ventral neurons (s-LNv), which control freerunning rhythmicity, with increased complexity and defects indicative of defective axonal function, which are present in late larval and early pupal stages. Spatial mapping reveals loss of CYC in neurons other than the s-LNvs contributes to this defect. However, the adult behavioural phenotype of a developmental CYC deficit is also associated with apparent defects in other clock neurons and expression markers for other clock-gene-expressing neurons indicate that developmental specification of these cells is altered in the absence of CYC. CYC mutants display a nocturnal profile in light-dark cycles, which cannot be rescued by adult-specific CYC. Nocturnality is a circuit property independent of s-LNvs, or the neuropeptide that bolsters s-LNv function, pigment-dispersing factor (PDF), which can be overriden by developmental CYC expression within s-LNvs.

I characterised a network state, driven by continued photic stimulation via the visual pathway, histamine signalling and large lateral ventral neurons (l-LNvs) which, in the absence of activation of a blue-light photoreceptor, CRY, encoded by the cryptochrome gene, which allows autonomous light sensitivity in clock-gene-expressing cells, results in a hierarchical shift in which s-LNvs, and the neuropeptide through which they interact with other clock neurons, PDF, are dispensible for behavioural rhythms. Behaviour is not rescued in this network state following developmental CYC loss, echoing additional defects beyond the PDF cells, though developmental CYC rescue in PDF-negative clock cells can restore rhythmicity in this condition.
University of Southampton
Hull, Alexander James
ab9bea9f-b15c-473d-8aaf-224e6b9eb4ae
Hull, Alexander James
ab9bea9f-b15c-473d-8aaf-224e6b9eb4ae
Wijnen, Herman
67e9bc5d-de6e-44ec-b4c2-50b67c5bc79d

Hull, Alexander James (2018) Developmental requirements and network properties of the Drosophila circadian clock circuit. University of Southampton, Doctoral Thesis, 386pp.

Record type: Thesis (Doctoral)

Abstract

CLOCK/CYCLE (CLK/CYC) and PERIOD/TIMELESS (PER/TIM) are heterodimers which cyclically inhibit one another transcriptionally and post-translationally, required in adult Drosophila for the molecular oscillation controlling daily rhythms in activity. Prior work in the lab established that developmental reduction of PER and subsequent adult reintroduction does not affect adult rhythmic behaviour, whilst developmental PER overexpression or CYC reduction does. I sought to characterise the developmental role of CYC. Developmental CYC reduction specific to metamorphosis can impact adult behavioural rhythms, but CYC restriction throughout development does not appear to disrupt adult molecular rhythms. Developmental CYC restriction results aberrant neuroanatomy of small lateral ventral neurons (s-LNv), which control freerunning rhythmicity, with increased complexity and defects indicative of defective axonal function, which are present in late larval and early pupal stages. Spatial mapping reveals loss of CYC in neurons other than the s-LNvs contributes to this defect. However, the adult behavioural phenotype of a developmental CYC deficit is also associated with apparent defects in other clock neurons and expression markers for other clock-gene-expressing neurons indicate that developmental specification of these cells is altered in the absence of CYC. CYC mutants display a nocturnal profile in light-dark cycles, which cannot be rescued by adult-specific CYC. Nocturnality is a circuit property independent of s-LNvs, or the neuropeptide that bolsters s-LNv function, pigment-dispersing factor (PDF), which can be overriden by developmental CYC expression within s-LNvs.

I characterised a network state, driven by continued photic stimulation via the visual pathway, histamine signalling and large lateral ventral neurons (l-LNvs) which, in the absence of activation of a blue-light photoreceptor, CRY, encoded by the cryptochrome gene, which allows autonomous light sensitivity in clock-gene-expressing cells, results in a hierarchical shift in which s-LNvs, and the neuropeptide through which they interact with other clock neurons, PDF, are dispensible for behavioural rhythms. Behaviour is not rescued in this network state following developmental CYC loss, echoing additional defects beyond the PDF cells, though developmental CYC rescue in PDF-negative clock cells can restore rhythmicity in this condition.

Text
Alex Hull FINAL thesis - Version of Record
Restricted to Repository staff only until 18 June 2021.
Available under License University of Southampton Thesis Licence.

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Published date: 30 June 2018

Identifiers

Local EPrints ID: 428656
URI: http://eprints.soton.ac.uk/id/eprint/428656
PURE UUID: a3236f4a-2a97-4ec1-82f8-82774f905ae3
ORCID for Herman Wijnen: ORCID iD orcid.org/0000-0002-8710-5176

Catalogue record

Date deposited: 05 Mar 2019 17:30
Last modified: 30 Jan 2020 01:38

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Contributors

Author: Alexander James Hull
Thesis advisor: Herman Wijnen ORCID iD

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