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 receptors. However, little is known about how NMDA receptors carry out this role. Here we report the first genes shown to be regulated by physiological levels of NMDA receptor function in developing neurons in vivo: NMDA receptor-regulated gene 1 (NARG1), NARG2, and NARG3. These genes share several striking regulatory features. All three are expressed at high levels in the neonatal brain in regions of neuronal proliferation and migration, are dramatically down-regulated during early postnatal development, and are down-regulated by NMDA receptor function. NARG2 and NARG3 appear to be novel, while NARG1 is the mammalian homologue of a yeast N-terminal acetyltransferase that regulates entry into the G(o) phase of the cell cycle. The results suggest that highly specific NMDA receptor-dependent regulation of gene expression plays an important role in the transition from proliferation of neuronal precursors to differentiation of neurons.
Sugiura
N
N
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA.
Patel
R G
RG
Corriveau
R A
RA
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology*; D002453:Cell Cycle; D002455:Cell Division; D002465:Cell Movement; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004330:Drosophila; D020224:Expressed Sequence Tags; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism* / Q000502:physiology; D012260:Ribonucleases / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D013997:Time Factors; D014018:Tissue Distribution; D015854:Up-Regulation; D014981:Xenopus
D018076:DNA, Complementary; C427761:Naa15 protein, mouse; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; D000123:Acetyltransferases; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D012260:Ribonucleases