Lef1/Tcf transcription factors together with β-catenin activate genes involved in 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, its transcriptional activity, however, remains elusive. We observed that in the adult brain Lef1 and β-catenin accumulate specifi cally in the nuclei of thalamic neurons, implying their involvement in regulating gene expression in these cells. The electrophysiological properties of thalamic cells depend on T-type low-voltage-gated Ca2+ channels. Since Cav3.1 is the predominant T-type pore subunit in the thalamus, we hypothesized that the Lef1/β-catenin complex regulates transcription of its gene. The increase of Cav3.1 gene expression in thalamic cells treated in vitro with Wnt3A, an activator of β-catenin, corroborated our presumption. Analysis of the Cav3.1 gene promoter revealed that its proximal region contains a Lef1 binding site. Indeed, luciferase assays confi rm that the promoter is activated by Lef1 and β-catenin. Furthermore, chromatin immunoprecipitation demonstrated that the promoter is occupied by β-catenin in the thalamus. Together, our data indicate that the Lef1/β-catenin complex regulates transcription of Cav3.1 gene. We propose that β-catenin contributes to neuronal excitability not only by a local action at the synapse, but also by activating gene expression.
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