TY - JOUR T1 - LEF1/β-Catenin Complex Regulates Transcription of the Cav3.1 Calcium Channel Gene (<em>Cacna1g</em>) in Thalamic Neurons of the Adult Brain JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4957 LP - 4969 DO - 10.1523/JNEUROSCI.1425-09.2010 VL - 30 IS - 14 AU - Marta B. Wisniewska AU - Katarzyna Misztal AU - Wojciech Michowski AU - Marcin Szczot AU - Elzbieta Purta AU - Wieslawa Lesniak AU - Monika E. Klejman AU - Michal Dabrowski AU - Robert K. Filipkowski AU - Andrzej Nagalski AU - Jerzy W. Mozrzymas AU - Jacek Kuznicki Y1 - 2010/04/07 UR - http://www.jneurosci.org/content/30/14/4957.abstract N2 - β-Catenin, together with LEF1/TCF transcription factors, activates genes involved in the proliferation and differentiation of neuronal precursor cells. In mature neurons, β-catenin participates in dendritogenesis and synaptic function as a component of the cadherin cell adhesion complex. However, the transcriptional activity of β-catenin in these cells remains elusive. In the present study, we found that in the adult mouse brain, β-catenin and LEF1 accumulate in the nuclei of neurons specifically in the thalamus. The particular electrophysiological properties of thalamic neurons depend on T-type calcium channels. Cav3.1 is the predominant T-type channel subunit in the thalamus, and we hypothesized that the Cacna1g gene encoding Cav3.1 is a target of the LEF1/β-catenin complex. We demonstrated that the expression of Cacna1g is high in the thalamus and is further increased in thalamic neurons treated in vitro with LiCl or WNT3A, activators of β-catenin. Luciferase reporter assays confirmed that the Cacna1G promoter is activated by LEF1 and β-catenin, and footprinting analysis revealed four LEF1 binding sites in the proximal region of this promoter. Chromatin immunoprecipitation demonstrated that the Cacna1g proximal promoter is occupied by β-catenin in vivo in the thalamus, but not in the hippocampus. Moreover, WNT3A stimulation enhanced T-type current in cultured thalamic neurons. Together, our data indicate that the LEF1/β-catenin complex regulates transcription of Cacna1g and uncover a novel function for β-catenin in mature neurons. We propose that β-catenin contributes to neuronal excitability not only by a local action at the synapse but also by activating gene expression in thalamic neurons. ER -