GABA-Induced GnRH Release Triggers Chordate Metamorphosis

Metamorphosis, a widespread life history strategy in metazoans, allows dispersal and use of different ecological niches through a dramatic body change from a larval stage [1Gilbert S.F. Developmental Biology.Eighth Edition. Sinauer Associates, 2006Google Scholar, 2Holstein T.W. Laudet V. Life-history evolution: at the origins of metamorphosis.Curr. Biol. 2014; 24: R159-R161Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar]. Despite its conservation and importance, the molecular mechanisms underlying its initiation and progression have been characterized in only a few animal models. In this study, through pharmacological and gene functional analyses, we identified neurotransmitters responsible for metamorphosis of the ascidian Ciona. Ciona metamorphosis converts swimming tadpole larvae into vase-like, sessile adults. Here, we show that the neurotransmitter GABA is a key regulator of metamorphosis. We found that gonadotropin-releasing hormone (GnRH) is a downstream neuropeptide of GABA. Although GABA is generally thought of as an inhibitory neurotransmitter, we found that it positively regulates secretion of GnRH through the metabotropic GABA receptor during Ciona metamorphosis. GnRH is necessary for reproductive maturation in vertebrates, and GABA is an important excitatory regulator of GnRH in the hypothalamus during puberty [3DeFazio R.A. Heger S. Ojeda S.R. Moenter S.M. Activation of A-type gamma-aminobutyric acid receptors excites gonadotropin-releasing hormone neurons.Mol. Endocrinol. 2002; 16: 2872-2891Crossref PubMed Scopus (248) Google Scholar, 4Han S.K. Abraham I.M. Herbison A.E. Effect of GABA on GnRH neurons switches from depolarization to hyperpolarization at puberty in the female mouse.Endocrinology. 2002; 143: 1459-1466Crossref PubMed Scopus (156) Google Scholar]. Our findings reveal another role of the GABA-GnRH axis in the regulation of post-embryonic development in chordates.