title: Eph/ephrin-B-mediated cell-to-cell interactions govern MTS20(+) thymic epithelial cell development.
abstract: Thymus development is a complex process in which cell-to-cell interactions between thymocytes and thymic epithelial cells (TECs) are essential to allow a proper maturation of both thymic cell components. Although signals that control thymocyte development are well known, mechanisms governing TEC maturation are poorly understood, especially those that regulate the maturation of immature TEC populations during early fetal thymus development. In this study, we show that EphB2-deficient, EphB2LacZ and EphB3-deficient fetal thymuses present a lower number of cells and delayed maturation of DN cell subsets compared to WT values. Moreover, deficits in the production of chemokines, known to be involved in the lymphoid seeding into the thymus, contribute in decreased proportions of intrathymic T cell progenitors (PIRA/B(+)) in the mutant thymuses from early stages of development. These features correlate with increased proportions of MTS20(+) cells but fewer MTS20(-) cells from E13.5 onward in the deficient thymuses, suggesting a delayed development of the first epithelial cells. In addition, in vitro the lack of thymocytes or the blockade of Eph/ephrin-B-mediated cell-to-cell interactions between either thymocytes-TECs or TECs-TECs in E13.5 fetal thymic lobes coursed with increased proportions of MTS20(+) TECs. This confirms, for the first time, that the presence of CD45(+) cells, corresponding at these stages to DN1 and DN2 cells, and Eph/ephrin-B-mediated heterotypic or homotypic cell interactions between thymocytes and TECs, or between TECs and themselves, contribute to the early maturation of MTS20(+) TECs.
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, C/José Antonio Novais 2, 28040, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Montero-Herradón
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, C/José Antonio Novais 2, 28040, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Ceca
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, C/José Antonio Novais 2, 28040, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez Del Collado
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, C/José Antonio Novais 2, 28040, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Alfaro
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, C/José Antonio Novais 2, 28040, Madrid, Spain. zapata@bio.ucm.es.
authors.forename: Agustín G
authors.identifier: http://orcid.org/0000-0003-0576-2672
authors.initials: AG
authors.lastname: Zapata
mesh_terms: D000818:Animals; D036388:Ephrin-B2 / Q000172:deficiency / Q000378:metabolism*; D036389:Ephrin-B3 / Q000172:deficiency / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051379:Mice; D018345:Mice, Knockout; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D036388:Ephrin-B2; D036389:Ephrin-B3
keywords: Eph/ephrins; Thymic epithelial cells; Thymocytes; Thymus development