Neuropeptide signalling in Placozoa

CECE 2026 – Barcelona

Gáspár Jékely

Centre for Organismal Studies, Heidelberg University

@jekely@biologists.social

Placozoa – no synapses, many peptides

Trichoplax adhaerens

  • placozoans - simplest animals
  • no neurons, no muscles
  • upper and lower ciliated epithelium
  • many neuropeptide-like molecules

  • few morphological cell types

Placozoa – no synapses, many peptides

  • neuropeptides are expressed in specific cell populations
  • non-overlapping expression
  • over 30 proneuropeptides

  • peptidergic cells tile the epithelium

The GPCR universe

Matching peptides with receptors – deorphanisation

Large-scale GPCR-peptide screen in placozoans

  • 27 predicted neuropeptide precursors
  • 104 class A GPCRs screened
  • 19 receptors activated by 13 mature peptides

Peptide-receptor interaction networks




Independent diversification of receptor-peptide systems


  • at least 8 ancestral cnidarian families of peptide GPCRs
  • independent divergence from bilaterian receptors
  • no one-to-one orthologs to bilaterians
  • prediction of receptor-ligand pairs across many cnidarians

Map to single-cell data

Organisation of peptidergic signalling

HCR to spatially map receptor-ligand pairs

HCR to spatially map receptor-ligand pairs

Some peptides induce long-term oscillations

Origin of the nervous system as a reflex arc?

George Howard Parker (1864 - 1955)

  • independent effectors evolved first
  • then receptor-effector systems
  • then organisation into nerve nets

Neuronal communication by chemical signals?



  • argued against the “connectionist view”
  • proposed instead that neurons could communicate by specific chemical signals
  • like a radio broadcast
  • chemicals diffuse through the nervous system
  • detected by specific chemical receptors in the target cells
  • communications could occur in the absence of synaptic transmission
  • discovery of pituitary hormones (1950ies)

Paul Alfred Weiss (1898 – 1989)

Chemical signalling between cells

  • some cells release a chemical (e.g. short peptide)
  • other cells express a specific receptor for the chemical
  • receptor activation -> change in cell state
  • a specific cell-to-cell signalling is possible
  • no synaptic connection

The chemical brain hypothesis

  • several cell types, each expressing a different peptide
  • specific receptors expressed in target cells

  • chemical ‘wiring diagram’
  • no synaptic connection
  • can be arbitrarily complex

Were the first nervous systems chemically wired?




Budd & Jékely


Detlev Arendt


Dickinsonia costata

Acknowledgements

  • Alexandra Kerbl
  • Karel Mocaer
  • Sanja Jasek
  • David Hug
  • Jules Duruz
  • Mateusz Kostecki
  • Benedikt Dürr
  • Kata Szabó
  • Marzia Matejcek
  • Ana Verbanac
  • Emily Savage
  • Simone Wolters
  • Anja Ciprianidis
  • Kevin Urbansky

Alumni

  • Kei Jokura (NIBB, Okazaki)
  • Luis Bezares (LBDV, Villefranche-sur-mer)
  • Luis Yanez-Guerra (Southampton)
  • Emelie Brodrick (Sussex)
  • Csaba Verasztó (EPFL)

Facilities

  • Réza Shahidi
  • Charlotta Funaya
  • Ulrike Engel