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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 modul...

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Main Authors: Everlien, Isabelle (Author) , Yen, Ting-Yun (Author) , Liu, Yu-Chao (Author) , Di Marco, Barbara (Author) , Vázquez-Marín, Javier (Author) , Centanin, Lázaro (Author) , Alfonso, Julieta (Author) , Monyer, Hannah (Author)
Format: Article (Journal)
Language:English
Published: 5 October 2022
In: Neuron
Year: 2022, Volume: 110, Issue: 19, Pages: 3139-3153.e6
ISSN:1097-4199
DOI:10.1016/j.neuron.2022.07.022
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.neuron.2022.07.022
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0896627322006675
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Author Notes:Isabelle Everlien, Ting-Yun Yen, Yu-Chao Liu, Barbara Di Marco, Javier Vázquez-Marín, Lázaro Centanin, Julieta Alfonso, Hannah Monyer
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Summary: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 intermediate 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 γ2 subunits. DBI’s modulatory effect parallels that of GABAA-receptor-mediating signaling in these cells in the proliferative areas, reflecting the tight control that DBI exerts on embryonic neurogenesis.
Item Description:Online verfügbar 22 August 2022, Artikelversion 5 Oktober 2022
Gesehen am 18.01.2023
Physical Description:Online Resource
ISSN:1097-4199
DOI:10.1016/j.neuron.2022.07.022

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