TY - JOUR
T1 - Indispensability of the glutamate transporters GLAST and GLT1 to brain development
AU - Matsugami, Toshiko R.
AU - Tanemura, Kentaro
AU - Mieda, Michihiro
AU - Nakatomi, Reiko
AU - Yamada, Keiko
AU - Kondo, Takashi
AU - Ogawa, Masaharu
AU - Obata, Kunihiko
AU - Watanabe, Masahiko
AU - Hashikawa, Tsutomu
AU - Tanaka, Kohichi
PY - 2006/8/8
Y1 - 2006/8/8
N2 - 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.
AB - 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.
KW - Axon/dendrite development
KW - Cortex
KW - Radial fiber
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U2 - 10.1073/pnas.0509144103
DO - 10.1073/pnas.0509144103
M3 - Article
C2 - 16880397
AN - SCOPUS:33747042753
SN - 0027-8424
VL - 103
SP - 12161
EP - 12166
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 32
ER -