Ectopic activation of GABAB receptors inhibits neurogenesis and metamorphosis in the cnidarian Nematostella vectensis

Shani Levy, Vera Brekhman, Anna Bakhman, Assaf Malik, Arnau Sebé-Pedrós, Mickey Kosloff, Tamar Lotan

Research output: Contribution to journalArticlepeer-review

Abstract

The metabotropic gamma-aminobutyric acid B receptor (GABABR) is a G protein-coupled receptor that mediates neuronal inhibition by the neurotransmitter GABA. While GABABR-mediated signalling has been suggested to play central roles in neuronal differentiation and proliferation across evolution, it has mostly been studied in the mammalian brain. Here, we demonstrate that ectopic activation of GABABR signalling affects neurogenic functions in the sea anemone Nematostella vectensis. We identified four putative Nematostella GABABR homologues presenting conserved three-dimensional extracellular domains and residues needed for binding GABA and the GABABR agonist baclofen. Moreover, sustained activation of GABABR signalling reversibly arrests the critical metamorphosis transition from planktonic larva to sessile polyp life stage. To understand the processes that underlie the developmental arrest, we combined transcriptomic and spatial analyses of control and baclofen-treated larvae. Our findings reveal that the cnidarian neurogenic programme is arrested following the addition of baclofen to developing larvae. Specifically, neuron development and neurite extension were inhibited, resulting in an underdeveloped and less organized nervous system and downregulation of proneural factors including NvSoxB(2), NvNeuroD1 and NvElav1. Our results thus point to an evolutionarily conserved function of GABABR in neurogenesis regulation and shed light on early cnidarian development.

Original languageEnglish
Pages (from-to)111-121
Number of pages11
JournalNature Ecology and Evolution
Volume5
Issue number1
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
We thank F. Rentzsch for providing the NvElav1 reporter line. We thank the Bioinformatics Service Unit at the University of Haifa and, specifically, N. Sher and M. Lalzar for their assistance. We thank S. Ben-Tabou de-Leon for helpful comments. This work was supported by the Israel Ministry of Science and Technology (grant no. 3-8774), the Israel Science Foundation (grant nos. 1454/13, 2155/15 and 3512/19) and the DS Research Centre at the University of Haifa.

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Ecology

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