Vesicular Glutamate Release Is Necessary for Neural Tube Formation

Abstract

The brain and spinal cord originate from a neural tube that is preceded by a flat structure known as the neural plate during early embryogenesis. In humans, failure of the neural plate to convert into a tube by the fourth week of pregnancy leads to neural tube defects (NTDs), birth defects with serious neurological consequences. The signaling mechanisms governing the process of neural tube morphogenesis are unclear. Here we show that in Xenopus laevis embryos, glutamate is released during neural plate folding in a Ca 2+ and vesicular glutamate transporter-1 (VGluT1)-dependent manner. Vesicular release of glutamate elicits Ca 2+ transients in neural plate cells that correlate with activation of Erk1/2. Knocking down or out VGluT1, globally or neural tissue-specifically, leads to NTDs and increased expression of Sox2, neural stem cell transcription factor, and neural plate cell proliferation. Exposure during early pregnancy to neuroactive drugs that disrupt these signaling mechanisms might increase the risk of NTDs in offspring.