title: Cutting Edge: β-Catenin-Interacting Tcf1 Isoforms Are Essential for Thymocyte Survival but Dispensable for Thymic Maturation Transitions.
abstract: T cell factor 1 (Tcf1) is essential for T cell development; however, it remains controversial whether β-catenin, a known coactivator of Tcf1, has a role. Tcf1 is expressed in multiple isoforms in T lineage cells, with the long isoforms interacting with β-catenin through an N-terminal domain. In this study, we specifically ablated Tcf1 long isoforms in mice (p45-/-mice) to abrogate β-catenin interaction. Although thymic cellularity was diminished in p45-/-mice, transition of thymocytes through the maturation stages was unaffected, with no overt signs of developmental blocks. p45-/-thymocytes showed increased apoptosis and alterations in transcriptome, but these changes were substantially more modest than in thymocytes lacking all Tcf1 isoforms. These data indicate that Tcf1-β-catenin interaction is necessary for promoting thymocyte survival to maintain thymic output. Rather than being dominant-negative regulators, Tcf1 short isoforms are adequate in supporting developing thymocytes to traverse through maturation steps and in regulating the expression of most Tcf1 target genes.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
authors.forename: Zhe
authors.identifier: 0000-0002-3338-4229
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
authors.forename: Shaojun
authors.identifier: 0000-0003-0777-2196
authors.initials: S
authors.lastname: Xing
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shan
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242.|Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, IA 52242.
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Gullicksrud
authors.affiliation: Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242; and.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Bair
authors.affiliation: Transgenic Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Du
authors.affiliation: Transgenic Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Chengyu
authors.identifier: 0000-0002-5136-9225
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242; hai-hui-xue@uiowa.edu.|Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, IA 52242.
authors.forename: Hai-Hui
authors.initials: HH
authors.lastname: Xue
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D060168:Thymocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*; D059467:Transcriptome; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D051822:T Cell Transcription Factor 1; D051176:beta Catenin