Article abstract
Nature Neuroscience 7, 510 - 517 (2004)
Published online: 4 April 2004 | doi:10.1038/nn1221
Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates
Leping Cheng1,2,9, Akiko Arata3,9, Rumiko Mizuguchi4,9, Ying Qian1,2, Asanka Karunaratne4, Paul A Gray1,2, Satoru Arata5, Senji Shirasawa6, Maxime Bouchard7, Ping Luo1,2, Chih-Li Chen1,2, Meinrad Busslinger7, Martyn Goulding4, Hiroshi Onimaru8 & Qiufu Ma1,2
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.
- The Dana-Farber Cancer Institute, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
- Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
- Laboratory for Memory and Learning, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
- Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
- Center for Biotechnology, Showa University, Tokyo 142-8555, Japan.
- Department of Pathology, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
- Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
- Department of Physiology, Showa University School of Medicine, Tokyo 142-8555, Japan.
- These authors contributed equally to this work.
Correspondence to: Qiufu Ma1,2 e-mail: Qiufu_Ma@dfci.harvard.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Tlx genes make an exciting choiceNature Neuroscience News and Views (01 May 2004)
Stem cells that know their placeNature Neuroscience News and Views (01 Dec 2002)
RESEARCH
Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypesNature Neuroscience Article (01 Nov 2005)
Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneuronsNature Neuroscience Article (01 Jun 2006)
See all 48 matches for Research
