title: From the Cover: Indispensability of the glutamate transporters GLAST and GLT1 to brain development.
abstract: Previous in vitro studies have shown that the neurotransmitter glutamate is important in brain development. Paradoxically, loss-of-function mouse models of glutamatergic signaling that are generated by genetic deletion of glutamate receptors or glutamate release show normal brain assembly. We examined the direct consequences on brain development of extracellular glutamate buildup due to the depletion of the glutamate transporters GLAST and GLT1. GLAST/GLT1 double knockout mice show multiple brain defects, including cortical, hippocampal, and olfactory bulb disorganization with perinatal mortality. Here, we report abnormal formation of the neocortex in GLAST/GLT1 mutants. Several essential aspects of neuronal development, such as stem cell proliferation, radial migration, neuronal differentiation, and survival of SP neurons, were impaired. These results provide direct in vivo evidence that GLAST and GLT1 are necessary for brain development through regulation of extracellular glutamate concentration and show that an important mechanism is likely to be maintenance of glutamate-mediated synaptic transmission.
authors.affiliation: Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Toshiko R
authors.initials: TR
authors.lastname: Matsugami
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanemura
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mieda
authors.forename: Reiko
authors.initials: R
authors.lastname: Nakatomi
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ogawa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Obata
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hashikawa
authors.forename: Kohichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology* / Q000473:pathology / Q000502:physiology*; D002540:Cerebral Cortex / Q000473:pathology; D003712:Dendrites / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1 / Q000502:physiology*; D027342:Excitatory Amino Acid Transporter 2 / Q000502:physiology*; D017353:Gene Deletion; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000378:metabolism
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid