Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates

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Title Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates
Author Cheng, Leping; Arata, Akiko; Mizuguchi, Rumiko; Qian, Ying; Karunaratne, Asanka; Gray, Paul A; Arata, Satoru; Shirasawa, Senji; Bouchard, Maxime; Luo, Ping; Chen, Chih-Li; Busslinger, Meinrad; Goulding, Martyn; Onimaru, Hiroshi; Ma, Qiufu
Journal Name Nature Neuroscience
Year Published 2004
Place of publication United States
Publisher Nature Publishing Group
Abstract Glutamatergic and GABAergic neurons mediate much of the excitatory and inhibitory neurotransmission, respectively, in the vertebrate nervous system. The process by which developing neurons select between these two cell fates is poorly understood. Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in the mouse dorsal spinal cord. First, we found that Tlx3 was required for specification of, and expressed in, glutamatergic neurons. Both generic and region-specific glutamatergic markers, including VGLUT2 and the AMPA receptor Gria2, were absent in Tlx mutant dorsal horn. Second, spinal GABAergic markers were derepressed in Tlx mutants, including Pax2 that is necessary for GABAergic differentiation, Gad1/2 and Viaat that regulate GABA synthesis and transport, and the kainate receptors Grik2/3. Third, ectopic expression of Tlx3 was sufficient to suppress GABAergic differentiation and induce formation of glutamatergic neurons. Finally, excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in Tlx3 mutant mice.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.nature.com/neuro/
Alternative URI http://dx.doi.org/10.1038/nn1221
Volume 7
Issue Number 5
Page from 510
Page to 517
ISSN 1097-6256
Date Accessioned 2006-07-25
Language en_AU
Faculty Faculty of Science, Environment, Engineering and Technology
Subject PRE2009-Neurogenetics
URI http://hdl.handle.net/10072/27295
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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