Signaling via GABAB receptors regulates early development and neurogenesis in the basal metazoan Nematostella vectensis

The metabotropic gamma-amino-butyric acid B receptor (GABA B R) is a G protein-coupled receptor that mediates neuronal inhibition by the neurotransmitter GABA. Here, we identified putative GABA B receptors and signaling modulators in the basal sea anemone Nematostella vectensis . Activation of GABA B R signaling reversibly arrests planula-to-polyp transformation during early development and affects the neurogenic program. We identified four Nematostella GABA B R homologs that have the conserved 3D extracellular domains and residues needed for binding of GABA and the GABA B R agonist baclofen. Transcriptomic analysis, combined with spatial analysis of baclofen-treated planulae, revealed that baclofen down-regulated pro-neural factors such as NvSoxB(2) , NvNeuroD1 and NvElav1 . Baclofen also inhibited neuron development and extended neurites, resulting in an under-developed and less organized nervous system. Our results shed light on cnidarian development and suggest an evolutionarily conserved function for GABA B R in regulation of neurogenesis, highlighting Nematostella as a new model system to study GABA B R signaling.