N-methyl-D-aspartate receptors regulate a group of transiently expressed genes in the developing brain

Mammalian brain development requires the transmission of electrical signals between neurons via the N-methyl-D-aspartate (NMDA) class of glutamate rec eptors. However, little is known about how NMDA receptors carry out this ro le. Here we report the first genes shown to be regulated by physiological l evels of NMDA receptor function in developing neurons in vivo: NMDA recepto r-regulated gene 1 (NARG1), NARG2, and NARG3. These genes share several str iking regulatory features. All three are expressed at high levels in the ne onatal brain in regions of neuronal proliferation and migration, are dramat ically down-regulated during early postnatal development, and are down-regu lated by NMDA receptor function. NARG2 and NARG3 appear to be novel, while NARG1 is the mammalian homologue of a yeast N-terminal acetyltransferase th at regulates entry into the G(o) phase of the cell cycle. The results sugge st that highly specific NMDA receptor-dependent regulation of gene expressi on plays an important role in the transition from proliferation of neuronal precursors to differentiation of neurons.