Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in themammalian central nervous system and acts via ionotropic (GABAA-Rs) and metabotropic(GABAB-Rs) receptors. GABAA-Rs are Cl- selective hetero-pentameric channels assembled bycombinations of 19 distinct gene products. Instead, GABAB-Rs are bi-subunit G-protein coupledreceptors linked to K+ or Ca2+ channels. Dysfunctions of GABA-signaling (GS) cause psychoticdisorders and correlate with epigenetic alterations, such as over-expression of DNA methyltransferase-1 which in turn imposes iper-methylation of GABA-regulated genes. The sea urchinembryo, which presents a rudimentary nervous system, offers a big opportunity to study the GSand its potential epigenetic implications in a simple eukaryote model. To this purpose, weperformed a comprehensive in silico analysis of the sea urchin genome and identified a 450 Kblong cluster containing two genes encoding for the GABAB-R subunits, and two genesrespectively encoding for a α/γ/ε-type and a β/ρ/δ/τ/π-type GABABA-R subunit. From anevolutionary perspective, this result revealed a unique genomic organization of these genes insea urchin. Next, to preliminarily evaluate the role of GS during development, Paracentrotuslividus embryos were cultured in the presence of GABA at concentrations ranging from 0.01 to1.0 mM. Compared to controls, treated embryos showed aberrations in axial patterning, with adose-dependent effect. In particular, at 48 hours post-fertilization control embryos were normalbilateral symmetric plutei whereas GABA-treated embryos displayed a radial organization withsupranumerary spicules. Washout experiments allowed to determine that the period ofsensitivity is restricted from the blastula to the gastrula stage. Altogether, these results suggestthat dysregulation of GS affects the polarization of the ectoderm. Although preliminary, thisstudy provide the first evidence of GS activity during development of echinoderms.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2012|