GABAA receptors and mother-derived taurine regulate neural progenitor cells specification in the mouse developing cortex. Mus musculus

The precise temporal regulation of the cellular properties of neural progenitor cells (NPCs) is essential for the histogenesis of the cerebral cortex. Neuroepithelial cells, the primary NPCs, transit to radial glia with astroglial properties. To coincide with this transition, NPCs start to differentiate into neurons, undergoing a switch from symmetric to asymmetric cell division. After the onset of neurogenesis, NPCs produce layer-specific neurons in a defined order. Here, we show that GABAA receptors and taurine are involved in this regulatory mechanism. Fetal exposure to GABAA blockers suppressed the transition to radial glia, the switch to asymmetric division and the differentiation into upper-layer neurons. Fetal exposure to GABAA positive modulators caused the opposite effects. Ca2+ imaging studies showed that NPCs principally responded to taurine, but not GABA, which is derived principally from mothers, before E13 via picrotoxin-sensitive receptors. Fetal exposure to GABAA receptor modulators resulted in considerable alterations in offspring behavior. Overall design: All animal manipulations were performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory animals 8th ed. revised 2011 and were approved by the Animal Research Committee of University of Fukui and Animal Care and Use Committee at the University of Tokushima. Care was taken to minimize the numbers, pain and suffering of animals throughout the experiments. Embryonic stages were calculated with the day of the vaginal plug detection as embryonic day 0 (E0). Timed-pregnant C57BL/6N mice (SLC Japan) received two intraperitoneal (i.p.) injections of either saline (control) or 8 mg/mL phenobarbital in saline (80 mg/kg ) twice a day, 6 h apart on E10-11. Embryos were removed from the pregnant mice that were sacrificed by cervical dislocation at E12.