GABAA Receptors and Maternally Derived Taurine Regulate the Temporal Specification of Progenitors of Excitatory Glutamatergic Neurons in the Mouse Developing Cortex

Temporal specification of the neural progenitors (NPs) producing excitatory glutamatergic neurons is essential for histogenesis of the cerebral cortex. Neuroepithelial cells, the primary NPs, transit to radial glia (RG). To coincide with the transition, NPs start to differentiate into neurons, undergoing a switch from symmetric to asymmetric cell division. After the onset of neurogenesis, NPs produce layer-specific neurons in a defined order with precise timing. Here, we show that GABA(A) receptors (GABA(A)Rs) and taurine are involved in this regulatory mechanism. Foetal exposure to GABA(A)R-antagonists suppressed the transition to RG, switch to asymmetric division, and differentiation into upper-layer neurons. Foetal exposure to GABA(A)R-agonists caused the opposite effects. Mammalian foetuses are dependent on taurine derived from the mothers. GABA and taurine function as endogenous ligands for GABA(A)Rs. Ca2+ imaging showed that NPs principally responded to taurine but not GABA before E13. The histological phenotypes of the taurine transporter knockout mice resembled those of the mice foetally exposed to GABA(A)R-antagonists. Foetal exposure to GABA(A)R-modulators resulted in considerable alterations in offspring behavior like core symptoms of autism. These results show that taurine regulates the temporal specification of NPs and that disrupting the taurine-receptor interaction possibly leads to neurodevelopmental disorders.

Automated summary

Temporal regulation of neural progenitors is essential for cortical histogenesis. GABA(A) receptors and taurine play a role in this regulation, with fetal exposure to modulators impacting offspring behavior. disruptions in taurine-receptor interaction may lead to neurodevelopmental disorders.