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- Title
Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes.
- Authors
Leping Cheng; Samad, Omar Abdel; Yi Xu; Mizuguchi, Rumiko; Ping Luo; Shirasawa, Senji; Goulding, Martyn; Qiufu Ma
- Abstract
Most neurons in vertebrates make a developmental choice between two principal neurotransmitter phenotypes (glutamatergic versus GABAergic). Here we show that the homeobox gene Lbx1 determines a GABAergic cell fate in the dorsal spinal cord at early embryonic stages. In Lbx1−/− mice, the presumptive GABAergic neurons are transformed into glutamatergic cells. Furthermore, overexpression of Lbx1 in the chick spinal cord is sufficient to induce GABAergic differentiation. Paradoxically, Lbx1 is also expressed in glutamatergic neurons. We previously reported that the homeobox genes Tlx1 and Tlx3 determine glutamatergic cell fate. Here we show that impaired glutamatergic differentiation, observed in Tlx3−/− mice, is restored in Tlx3−/−Lbx1−/− mice. These genetic studies suggest that Lbx1 expression defines a basal GABAergic differentiation state, and Tlx3 acts to antagonize Lbx1 to promote glutamatergic differentiation.
- Subjects
AMINO acid neurotransmitters; PHENOTYPES; GABA; NEURAL transmission; NEURONS; HOMEOBOX genes; NERVOUS system
- Publication
Nature Neuroscience, 2005, Vol 8, Issue 11, p1510
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn1569