Nitric-oxide-feedback to ciliary photoreceptor cells orchestrates UV avoidance in a peptidergic circuit in Platynereis

Neuropeptide Signaling: Bridging Cell Biology, Neurophysiology, and Behavior
April 16 - 19, 2023

Gáspár Jékely

Living Systems Institute, University of Exeter
Centre for Organismal Studies, University of Heidelberg

Emerging marine model organisms

Image: Patrick Steinmetz
Nematostella vectensis
Platynereis dumerilii
Trichoplax adhaerens

Placozoa – no synapses, many peptides

  • evolution of peptides and neurotransmitters

  • large-scale receptor deorphanisation

  • map chemical connectomes to scRNAseq

Large-scale GPCR-peptide screen in Nematostella

Mapping to single-cell data

A peptidergic connectome

Platynereis dumerilii







  • breeding culture, full life-cycle
  • embryos daily, year round
  • genome sequence
  • microinjection, transgenesis
  • neuron-specific promoters and antibodies
  • knock-out lines
  • neuronal connectome
  • whole-body neuronal activity imaging
  • whole-animal pharmacology by bath application 😎

Platynereis dumerilii















Spawning
movie by Albrecht Fischer


Synchronously developing larvae

UV response in Platynereis larvae

UV-responding brain ciliary photoreceptors (cPRCs)

No UV avoidance in c-opsin1 knockouts

No cPRC response in c-opsin1 knockouts

Whole-body volume EM of an entire three-day-old larva

The nervous system of the larva


~2,000 neurons

Synaptic connectome

Circuitry of ciliary photoreceptors





Circuitry of ciliary photoreceptors

Strong cPRC activation after UV exposure

Many peptides and modulators in the circuit

Multiplex immunogold for neuropeptides in the EM volume

Mapping of (pro)neuropeptides

Single-cell data for cPRC cells and their interneurons

::: footer Kei Jokura :::

Nitric-oxyde synthase in postsynaptic interneurons

HCR                        Transgenic labelling

NO is produced in the neuropil after UV stimulation

NOS mutants have altered cPRC response

NOS mutants have altered INRGW and motoneuron response

NOS mutants show defective UV avoidance

Two unusual guanylyl cyclases in the cPRCs

NIT-GC1 RNA
NIT-GC1 protein
NIT-GC2 RNA
NIT-GC2 protein

Two unusual guanylyl cyclases in the cPRCs

NIT-GC morphants have altered circuit activity

Mathematical modelling of the circuit

Model fitting

wild type
NOS-11
NOS-23
NIT-GC2 mo.

Integration and memory of UV exposure

Integration and memory of UV exposure

Acknowledgements

  • Emelie Brodrick
  • Cyrielle Kaltenrieder
  • Réza Shahidi
  • Milena Marinkovic
  • Daniel Thiel
  • Sanja Jasek
  • Cameron Hird
  • Rebecca Turner
  • Luis A. Bezares-Calderón
  • Kei Jokura
  • Luis Yanez Guerra
  • Alexandra Kerbl

Former lab members

  • Albina Asadulina
  • James Beard
  • Markus Conzelmann
  • Nadine Randel
  • Philipp Bauknecht
  • Martin Gühmann
  • Cristina Pineiro-Lopez
  • Nobuo Ueda
  • Aurora Panzera
  • Csaba Verasztó
  • Elizabeth Williams

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