Diazepam binding inhibitor governs neurogenesis of excitatory and inhibitory neurons during embryonic development via GABA signaling

Of the neurotransmitters that influence neurogenesis, gamma-aminobutyric acid (GABA) plays an outstanding role, and GABA receptors support non-synaptic signaling in progenitors and migrating neurons. Here, we report that expression levels of diazepam binding inhibitor (DBI), an endozepine that modulates GABA signaling, regulate embryonic neurogenesis, affecting the long-term outcome regarding the number of neurons in the postnatal mouse brain. We demonstrate that DBI is highly expressed in radial glia and inter-mediate progenitor cells in the germinal zones of the embryonic mouse brain that give rise to excitatory and inhibitory cells. The mechanism by which DBI controls neurogenesis involves its action as a negative allosteric modulator of GABA-induced currents on progenitor cells that express GABAA receptors containing g2 sub-units. DBI's modulatory effect parallels that of GABAA-receptor-mediating signaling in these cells in the pro-liferative areas, reflecting the tight control that DBI exerts on embryonic neurogenesis.

Automated summary

In this study, it is found that the endozepine diazepam binding inhibitor (DBI) regulates embryonic neurogenesis by negatively modulating GABA-induced currents on progenitor cells. DBI's mechanism is similar to GABAA-receptor-mediated signaling and exerts tight control on embryonic neurogenesis.