GABAA Receptors and Maternally Derived Taurine Regulate the Temporal Specification of Progenitors of Excitatory Glutamatergic Neurons in the Mouse Developing Cortex. (17th May 2021)

• Record Type: Journal Article
• Authors: Tochitani, Shiro; Furukawa, Tomonori; Bando, Ryo; Kondo, Shigeaki; Ito, Takashi; Matsushima, Yoshitaka; Kojima, Toshio; Matsuzaki, Hideo; Fukuda, Atsuo
• Is Part Of: Cerebral cortex. Volume 31:Number 10(2021)
• Page Start: 4554
• Page End: 4575
• Publication Date: 2021-05-17
• Subjects: autistic phenotype -- developmental timer -- mother-fetus crosstalk -- neural stem cells -- placental transfer; Cerebral cortex -- Periodicals; Brain -- Periodicals; 612.825
• DOI: 10.1093/cercor/bhab106
• Languages: English
• ISSNs: 1047-3211

Abstract

Abstract: 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 GABAA receptors (GABAA Rs) and taurine are involved in this regulatory mechanism. Foetal exposure to GABAA R-antagonists suppressed the transition to RG, switch to asymmetric division, and differentiation into upper-layer neurons. Foetal exposure to GABAA R-agonists caused the opposite effects. Mammalian foetuses are dependent on taurine derived from the mothers. GABA and taurine function as endogenous ligands for GABAA Rs. Ca 2+ 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 GABAA R-antagonists. Foetal exposure to GABAA 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.