title: Entry into the thymic microenvironment triggers Notch activation in the earliest migrant T cell progenitors.
abstract: Interactions between T cell precursors and thymic stromal cells are essential during thymocyte development. However, the role of the thymus in initial commitment of lymphoid progenitors to the T lineage remains controversial, with data providing evidence for both extra- and intrathymic commitment mechanisms. In this context, it is clear that Notch1 is an important mediator during initiation of T cell development. Here we have analyzed the mechanisms regulating Notch activation in lymphoid precursors at extrathymic sites and in the thymus, including stages representing the first wave of embryonic thymus colonization on embryonic day 12 of gestation. We show that Notch activation in migrant lymphoid precursors requires entry into the thymic microenvironment where they are exposed to Notch ligands expressed by immature thymic epithelial cells. Moreover, continued Notch signaling in such precursors requires sustained interactions with Notch ligands. Collectively, these findings suggest a role for Notch in an intrathymic mechanism of T cell lineage commitment involving sustained interactions with Notch ligand bearing thymic epithelium.
authors.affiliation: Department of Anatomy, Medical Research Council Center for Immune Regulation, Division of Immunity and Infection, Medical School, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Harman
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jenkinson
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D005333:Fetus; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D051880:Receptors, Notch; D015398:Signal Transduction / Q000276:immunology; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch