Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the
mammalian central nervous system and acts via ionotropic (GABAA-Rs) and metabotropic
(GABAB-Rs) receptors. GABAA-Rs are Cl- selective hetero-pentameric channels assembled by
combinations of 19 distinct gene products. Instead, GABAB-Rs are bi-subunit G-protein coupled
receptors linked to K+ or Ca2+ channels. Dysfunctions of GABA-signaling (GS) cause psychotic
disorders and correlate with epigenetic alterations, such as over-expression of DNA methyl
transferase-1 which in turn imposes iper-methylation of GABA-regulated genes. The sea urchin
embryo, which presents a rudimentary nervous system, offers a big opportunity to study the GS
and its potential epigenetic implications in a simple eukaryote model. To this purpose, we
performed a comprehensive in silico analysis of the sea urchin genome and identified a 450 Kb
long cluster containing two genes encoding for the GABAB-R subunits, and two genes
respectively encoding for a \u3b1/\u3b3/\u3b5-type and a \u3b2/\u3c1/\u3b4/\u3c4/\u3c0-type GABA
B
A-R subunit. From an
evolutionary perspective, this result revealed a unique genomic organization of these genes in
sea urchin. Next, to preliminarily evaluate the role of GS during development, Paracentrotus
lividus embryos were cultured in the presence of GABA at concentrations ranging from 0.01 to
1.0 mM. Compared to controls, treated embryos showed aberrations in axial patterning, with a
dose-dependent effect. In particular, at 48 hours post-fertilization control embryos were normal
bilateral symmetric plutei whereas GABA-treated embryos displayed a radial organization with
supranumerary spicules. Washout experiments allowed to determine that the period of
sensitivity is restricted from the blastula to the gastrula stage. Altogether, these results suggest
that dysregulation of GS affects the polarization of the ectoderm. Although preliminary, this
study provide the first evidence of GS activity during development of echinoderms