title: Postnatal isoform switch and protein localization of LEF1 and TCF7L2 transcription factors in cortical, thalamic, and mesencephalic regions of the adult mouse brain.
abstract: β-Catenin signaling, leading to the activation of lymphoid enhancer-binding factor 1/T cell factor (LEF1/TCF) transcription factors, plays a well-established role in transcription regulation during development and tissue homeostasis. In the adult organism, the activity of this pathway has been found in stem cell niches and postmitotic thalamic neurons. Recently, studies show that mutations in components of β-catenin signaling networks have been associated with several psychiatric disorders, indicating the involvement of β-catenin and LEF1/TCF proteins in the proper functioning of the brain. Here, we report a comprehensive analysis of LEF1/TCF protein localization and the expression profile of their isoforms in cortical, thalamic, and midbrain regions in mice. We detected LEF1 and TCF7L2 proteins in neurons of the thalamus and dorsal midbrain, i.e., subcortical regions specialized in the integration of diverse sources of sensory information. These neurons also exhibited nuclear localization of β-catenin, suggesting the involvement of β-catenin/LEF1/TCF7L2 in the regulation of gene expression in these regions. Analysis of alternative splicing and promoter usage identified brain-specific TCF7L2 isoforms and revealed a developmentally coordinated transition in the composition of LEF1 and TCF7L2 isoforms. In the case of TCF7L2, the typical brain isoforms lack the so-called C clamp; in addition, the dominant-negative isoforms are predominant in the embryonic thalamus but disappear postnatally. The present study provides a necessary framework to understand the role of LEF1/TCF factors in thalamic and midbrain development until adulthood and predicts that the regulatory role of these proteins in the adult brain is significantly different from their role in the embryonic brain or other non-neural tissues.
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 4 Ks. Trojdena Street, 02-109, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Nagalski
authors.forename: M
authors.initials: M
authors.lastname: Irimia
authors.forename: L
authors.initials: L
authors.lastname: Szewczyk
authors.forename: J L
authors.initials: JL
authors.lastname: Ferran
authors.forename: K
authors.initials: K
authors.lastname: Misztal
authors.forename: J
authors.initials: J
authors.lastname: Kuznicki
authors.forename: M B
authors.initials: MB
authors.lastname: Wisniewska
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013788:Thalamus / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D017931:DNA Primers; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D020033:Protein Isoforms; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin