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Publication : Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes.

First Author  Cheng L Year  2005
Journal  Nat Neurosci Volume  8
Issue  11 Pages  1510-5
PubMed ID  16234809 Mgi Jnum  J:102513
Mgi Id  MGI:3607682 Doi  10.1038/nn1569
Citation  Cheng L, et al. (2005) Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes. Nat Neurosci 8(11):1510-5
abstractText  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.
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