On becoming a T cell, a convergence of factors kick it up a Notch along the way

Foss, 2001, The importation of hematogenous precursors by the thymus is a gated phenomenon in normal adult mice, J Exp Med, 193, 365, 10.1084/jem.193.3.365 Donskoy, 2003, Gated importation of prothymocytes by adult mouse thymus is coordinated with their periodic mobilization from bone marrow, J Immunol, 171, 3568, 10.4049/jimmunol.171.7.3568 Schwarz, 2004, Circulating hematopoietic progenitors with T lineage potential, Nat Immunol, 5, 953, 10.1038/ni1101 Lai, 2007, Identification of a bone marrow precursor of the earliest thymocytes in adult mouse, Proc Natl Acad Sci USA, 104, 6311, 10.1073/pnas.0609608104 Igarashi, 2002, Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow, Immunity, 17, 10.1016/S1074-7613(02)00366-7 Luc, 2007, Biological and molecular evidence for existence of lymphoid-primed multipotent progenitors, Ann NY Acad Sci, 1106, 89, 10.1196/annals.1392.023 Adolfsson, 2005, Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment, Cell, 121, 295, 10.1016/j.cell.2005.02.013 Kondo, 1997, Identification of clonogenic common lymphoid progenitors in mouse bone marrow, Cell, 91, 661, 10.1016/S0092-8674(00)80453-5 Gounari, 2002, Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene, Nat Immunol, 3, 489, 10.1038/ni778 Krueger, 2007, Identification of a T lineage-committed progenitor in adult blood, Immunity, 26, 105, 10.1016/j.immuni.2006.12.004 Porritt, 2004, Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages, Immunity, 20, 735, 10.1016/j.immuni.2004.05.004 Zlotoff, 2010, CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus, Blood, 115, 1897, 10.1182/blood-2009-08-237784 Krueger, 2010, CC chemokine receptor 7 and 9 double-deficient hematopoietic progenitors are severely impaired in seeding the adult thymus, Blood, 115, 1906, 10.1182/blood-2009-07-235721 Gossens, 2009, Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25, J Exp Med, 206, 761, 10.1084/jem.20082502 Uehara, 2002, A role for CCR9 in T lymphocyte development and migration, J Immunol, 168, 2811, 10.4049/jimmunol.168.6.2811 Schwarz, 2007, Selective thymus settling regulated by cytokine and chemokine receptors, J Immunol, 178, 2008, 10.4049/jimmunol.178.4.2008 Bhandoola, 2007, Commitment and developmental potential of extrathymic and intrathymic T cell precursors: plenty to choose from, Immunity, 26, 678, 10.1016/j.immuni.2007.05.009 Saran, 2010, Multiple extrathymic precursors contribute to T-cell development with different kinetics, Blood, 115, 1137, 10.1182/blood-2009-07-230821 Serwold, 2009, Reductive isolation from bone marrow and blood implicates common lymphoid progenitors as the major source of thymopoiesis, Blood, 113, 807, 10.1182/blood-2008-08-173682 Karsunky, 2008, Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages, Blood, 111, 5562, 10.1182/blood-2007-11-126219 Heinzel, 2007, Bone marrow-derived hemopoietic precursors commit to the T cell lineage only after arrival in the thymic microenvironment, J Immunol, 178, 858, 10.4049/jimmunol.178.2.858 Shortman, 1996, lymphocyte progenitors, Annu Rev Immunol, 14, 29, 10.1146/annurev.immunol.14.1.29 Petrie, 2007, Zoned out: functional mapping of stromal signaling microenvironments in the thymus, Annu Rev Immunol, 25, 649, 10.1146/annurev.immunol.23.021704.115715 Schmitt, 2004, Maintenance of T cell specification and differentiation requires recurrent notch receptor–ligand interactions, J Exp Med, 200, 469, 10.1084/jem.20040394 Maillard, 2005, Regulation of lymphoid development, differentiation, and function by the Notch signaling pathway, Annu Rev Immunol, 23, 945, 10.1146/annurev.immunol.23.021704.115747 Ciofani, 2007, The thymus as an inductive site for T lymphopoiesis, Annu Rev Cell Dev Biol, 23, 463, 10.1146/annurev.cellbio.23.090506.123547 Ciofani, 2005, Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism, Nat Immunol, 6, 881, 10.1038/ni1234 Yashiro-Ohtani, 2010, Notch regulation of early thymocyte development, Semin Immunol, 22, 261, 10.1016/j.smim.2010.04.015 Rothenberg, 2008, Launching the T-cell-lineage developmental programme, Nat Rev Immunol, 8, 9, 10.1038/nri2232 Dervovic, 2010, Positive selection of T cells, an in vitro view, Semin Immunol, 22, 276, 10.1016/j.smim.2010.04.014 Wong, 2010, γδ and αβ T cell lineage choice: resolution by a stronger sense of being, Semin Immunol, 22, 228, 10.1016/j.smim.2010.04.005 Takahama, 2006, Journey through the thymus: stromal guides for T-cell development and selection, Nat Rev Immunol, 6, 127, 10.1038/nri1781 Swiatek, 1994, Notch1 is essential for postimplantation development in mice, Genes Dev, 8, 707, 10.1101/gad.8.6.707 Conlon, 1995, Notch1 is required for the coordinate segmentation of somites, Development, 121, 1533, 10.1242/dev.121.5.1533 Bray, 2006, Notch signalling: a simple pathway becomes complex, Nat Rev Mol Cell Biol, 7, 678, 10.1038/nrm2009 Hozumi, 2008, Delta-like 4 is indispensable in thymic environment specific for T cell development, J Exp Med, 205, 2507, 10.1084/jem.20080134 Koch, 2008, Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment, J Exp Med, 205, 2515, 10.1084/jem.20080829 Besseyrias, 2007, Hierarchy of Delta–Notch interactions promoting T cell lineage commitment and maturation, J Exp Med, 204, 331, 10.1084/jem.20061442 Duarte, 2004, Dosage-sensitive requirement for mouse Dll4 in artery development, Genes Dev, 18, 2474, 10.1101/gad.1239004 Shutter, 2000, Dll4, a novel Notch ligand expressed in arterial endothelium, Genes Dev, 14, 1313, 10.1101/gad.14.11.1313 Hellstrom, 2007, Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis, Nature, 445, 776, 10.1038/nature05571 Mohtashami, 2010, Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes, J Immunol, 185, 867, 10.4049/jimmunol.1000782 Grifith, 2009, Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation, Immunity, 31, 999, 10.1016/j.immuni.2009.09.024 Radtke, 1999, Deficient T cell fate specification in mice with an induced inactivation of Notch1, Immunity, 25, 547, 10.1016/S1074-7613(00)80054-0 Abe, 2010, Notch ligands transduce different magnitudes of signaling critical for determination of T-cell fate, Eur J Immunol, 40, 1, 10.1002/eji.200940006 Varnum-Finney, 1998, The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells, Blood, 91, 4084, 10.1182/blood.V91.11.4084 Lehar, 2005, Notch ligands Delta 1 and Jagged1 transmit distinct signals to T-cell precursors, Blood, 105, 1440, 10.1182/blood-2004-08-3257 Dontje, 2006, Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B, Blood, 107, 2446, 10.1182/blood-2005-05-2090 Kovall, 2007, Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex, Curr Opin Struct Biol, 17, 117, 10.1016/j.sbi.2006.11.004 Lubman, 2007, Quantitative dissection of the Notch:CSL interaction: insights into the Notch-mediated transcriptional switch, J Mol Biol, 365, 577, 10.1016/j.jmb.2006.09.071 Engel, 2010, Myeloid translocation gene 16 (MTG16) interacts with Notch transcription complex components to integrate Notch signaling in hematopoietic cell fate specification, Mol Cell Biol, 30, 1852, 10.1128/MCB.01342-09 Deftos, 2000, Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes, Immunity, 13, 73, 10.1016/S1074-7613(00)00009-1 Reizis, 2002, Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway, Genes Dev, 16, 295, 10.1101/gad.960702 Visan, 2005, Regulation of intrathymic T-cell development by Lunatic Fringe–Notch1 interactions, Immunol Rev, 209, 76, 10.1111/j.0105-2896.2006.00360.x Visan, 2006, Regulation of T lymphopoiesis by Notch1 and Lunatic fringe-mediated competition for intrathymic niches, Nat Immunol, 7, 634, 10.1038/ni1345 Xiao, 2008, T cell development from kit-negative progenitors in the Foxn1Δ/Δ mutant thymus, J Immunol, 180, 914, 10.4049/jimmunol.180.2.914 Wilson, 2001, Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus, J Exp Med, 194, 1003, 10.1084/jem.194.7.1003 Han, 2002, Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision, Int Immunol, 14, 637, 10.1093/intimm/dxf030 Pui, 1999, Notch1 expression in early lymphopoiesis influences B versus T lineage determination, Immunity, 11, 299, 10.1016/S1074-7613(00)80105-3 Rodewald, 1994, Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization, EMBO, 13, 4229, 10.1002/j.1460-2075.1994.tb06743.x Carlyle, 1998, Requirement for the thymus in alphabeta T lymphocyte lineage commitment, Immunity, 9, 187, 10.1016/S1074-7613(00)80601-9 Harman, 2005, T/B lineage choice occurs prior to intrathymic Notch signaling, Blood, 106, 886, 10.1182/blood-2004-12-4881 Feyerabend, 2009, Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms, Immunity, 30, 1, 10.1016/j.immuni.2008.10.016 Maeda, 2007, Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF, Science, 316, 860, 10.1126/science.1140881 Hoflinger, 2004, Analysis of Notch1 function by in vitro T cell differentiation of Pax5 mutant lymphoid progenitors, J Immunol, 17, 3935, 10.4049/jimmunol.173.6.3935 Cobaleda, 2007, Pax5: the guardian of B cell identity and function, Nat Immunol, 8, 463, 10.1038/ni1454 Cobaleda, 2007, Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors, Nature, 449, 473, 10.1038/nature06159 Soubani, 2002, Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1, Immunity, 17, 781, 10.1016/S1074-7613(02)00472-7 Roessler, 2007, Distinct promoters mediate the regulation of Ebf1 gene expression by interleukin-7 and Pax5, Mol Cell Biol, 27, 579, 10.1128/MCB.01192-06 Treiber, 2010, Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription-independent posing of chromatin, Immunity, 32, 714, 10.1016/j.immuni.2010.04.013 Mendel, 2010, Transcription control of early B cell development, Curr Opin Immunol, 22, 161, 10.1016/j.coi.2010.01.010 Pongubala, 2008, Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5, Nat Immunol, 9, 203, 10.1038/ni1555 Boos, 2007, Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity, J Exp Med, 204, 1119, 10.1084/jem.20061959 Nie, 2008, Regulation of lymphocyte development by cell-type-specific interpretation of notch signals, Mol Cell Biol, 28, 2078, 10.1128/MCB.00844-07 Ikawa, 2006, E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment, J Exp Med, 203, 1329, 10.1084/jem.20060268 Yashiro-Ohtani, 2009, Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A, Genes Dev, 23, 1665, 10.1101/gad.1793709 Dias, 2008, E2A proteins promote development of lymphoid-primed multipotent progenitors, Immunity, 29, 217, 10.1016/j.immuni.2008.05.015 Dias, 2008, Transcriptional regulation of lymphocyte development, Curr Opin Genet Dev, 18, 1, 10.1016/j.gde.2008.07.015 Wang, 2010, Context-dependent regulation of hematopoietic lineage choice by HEBAlt, J Immunol, 185, 4109, 10.4049/jimmunol.0901783 Hoogenkamp, 2007, The Pu.1 locus is differentially regulated at the level of chromatin structure and noncoding transcription by alternate mechanisms at distinct developmental stages of hematopoiesis, Mol Cell Biol, 27, 7425, 10.1128/MCB.00905-07 Spooner, 2009, A recurrent network involving the transcription factors PU.1 and Gfi1 orchestrates innate and adaptive immune cell fates, Immunity, 31, 576, 10.1016/j.immuni.2009.07.011 Ng, 2009, Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells, Immunity, 30, 493, 10.1016/j.immuni.2009.01.014 Reynaud, 2008, Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangments by Ikaros, Nat Immunol, 9, 927, 10.1038/ni.1626 Thompson, 2007, Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits, Immunity, 26, 335, 10.1016/j.immuni.2007.02.010 Papathanasiou, 2009, Self-renewal of the long-term reconstituting subset of hematopoietic stem cells is regulated by Ikaros, Stem Cells, 27, 3082, 10.1002/stem.170 Chari, 2008, Ikaros regulates Notch target gene expression in developing thymocytes, J Immunol, 181, 6265, 10.4049/jimmunol.181.9.6265 Allman, 2003, Thymopoiesis independent of common lymphoid progenitors, Nat Immunol, 4, 168, 10.1038/ni878 Ting, 1996, Transcription factor GATA-3 is required for development of the T-cell lineage, Nature, 384, 474, 10.1038/384474a0 Hosoya, 2009, GATA-3 is required for early T lineage progenitor development, J Exp Med, 206, 2987, 10.1084/jem.20090934 Chen, 2001, Enforced expression of the GATA-3 transcription factor affects cell fate decisions in hematopoiesis, Exp Hematol, 29, 971, 10.1016/S0301-472X(01)00670-1 Taghon, 2007, Mast cell lineage diversion of T lineage precursors by the essential T-cell transcription factor GATA-3, Nat Immunol, 8, 845, 10.1038/ni1486 Hozumi, 2008, Notch signaling is necessary for GATA3 function in the initiation of T cell development, Eur J Immunol, 38, 977, 10.1002/eji.200737688 Schmitt, 2002, Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro, Immunity, 17, 749, 10.1016/S1074-7613(02)00474-0 Zuniga-Pflucker, 2004, T-cell development made simple, Nat Rev Immunol, 4, 67, 10.1038/nri1257 Bell, 2008, The earliest thymic progenitors for T cells possess myeloid lineage potential, Nature, 452, 764, 10.1038/nature06840 Wada, 2008, Adult T-cell progenitors retain myeloid potential, Nature, 452, 768, 10.1038/nature06839 Yui, 2010, Fine-scale staging of T cell lineage commitment in adult mouse thymus, J Immunol, 185, 284, 10.4049/jimmunol.1000679 Zhou, 2009, Notch and wingless signaling cooperate in regulation of dendritic cell differentiation, Immunity, 30, 845, 10.1016/j.immuni.2009.03.021 Catton, 2007, Notch-RBP-J signaling controls the homeostasis of CD8-dendritic cells in the spleen, J Exp Med, 204, 1653, 10.1084/jem.20062648 Malhotra, 2008, Contrasting responses of lymphoid progenitors to canonical and noncanonical Wnt signals, J Immunol, 181, 3955, 10.4049/jimmunol.181.6.3955 Carotta, 2010, The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner, Immunity, 32, 628, 10.1016/j.immuni.2010.05.005 Mercher, 2008, Notch signaling specifies megakaryocyte development from hematopoietic stem cells, Cell Stem Cell, 3, 314, 10.1016/j.stem.2008.07.010 Wolfler, 2010, Lineage-instructive function of C/EBPalpha in multipotent hematopoietic cells and early thymic progenitors, Blood, 116, 4116, 10.1182/blood-2010-03-275404 Sakata-Yanagimoto, 2008, Coordinated regulation of transcription factors through Notch2 is an important mediator of mast cell fate, Proc Natl Acad Sci USA, 105, 7839, 10.1073/pnas.0801074105 Huang, 2008, PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis, Nat Genet, 40, 51, 10.1038/ng.2007.7 Zarnegar, 2010, Cell-type specific activation and repression of PU.1 by a complex of discrete, functionally specialized cis-regulatory elements, Mol Cell Biol, 30, 4922, 10.1128/MCB.00354-10 Stehling-Sun, 2009, Regulation of lymphoid versus myeloid fate ‘choice’ by the transcription factor Mef2c, Nat Immunol, 10, 289, 10.1038/ni.1694 Franco, 2006, Notch/Delta signaling constraints reengineering of pro-T cells by PU.1, Proc Natl Acad Sci USA, 103, 11993, 10.1073/pnas.0601188103 Taghon, 2006, Developmental and molecular characterization of emerging beta- and gammadelta-selected pre-T cells in the adult mouse thymus, Immunity, 24, 53, 10.1016/j.immuni.2005.11.012 Zhou, 2008, Notch-dependent control of myelopoiesis is regulated by fucosylation, Blood, 112, 308, 10.1182/blood-2007-11-115204 Rothenberg, 2007, Negotiation of the T lineage fate decision by transcription-factor interplay and microenvironmental signals, Immunity, 26, 690, 10.1016/j.immuni.2007.06.005 Ikawa, 2010, An essential developmental checkpoint for production of the T cell lineage, Science, 329, 93, 10.1126/science.1188995 Li, 2010, An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b, Science, 329, 89, 10.1126/science.1188989 Carlyle, 1998, Lineage commitment and differentiation of T and natural killer lymphocytes in the fetal mouse, Immunol Rev, 165, 63, 10.1111/j.1600-065X.1998.tb01230.x Haraguchi, 2009, Notch activation induces the generation of functional NK cells form human cord blood CD34-positive cells devoid of IL-15, J Immunol, 182, 6168, 10.4049/jimmunol.0803036 Charoudeh, 2010, Identification of an NK/T cell-restricted progenitor in adult bone marrow contributing to bone marrow- and thymic-dependent NK cells, Blood, 116, 183, 10.1182/blood-2009-10-247130 Blom, 1999, Disruption of alphabeta but not gammadelta T cell development by overexpression of the helix-loop-helix protein Id3 in commited T cell progenitors, EMBO J, 18, 2793, 10.1093/emboj/18.10.2793 Schotte, 2010, Syngergy between IL-15 and Id2 promotes the expansion of human NK progenitor cells, which can be counteracted by the E protein HEB required to drive T cell development, J Immunol, 184, 6670, 10.4049/jimmunol.0901508 Kamath, 2008, Dose-dependent repression of T-cell and natural killer cell genes by PU.1 enforces myeloid and B-cell identity, Leukemia, 22, 1214, 10.1038/leu.2008.67 Ohno, 2008, Runx proteins are involved in regulation of CD122, Ly49 family and IFN-gamma expression during NK cell differentiation, Int Immunol, 20, 71, 10.1093/intimm/dxm120 Vosshenrich, 2006, A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127, Nat Immunol, 7, 1217, 10.1038/ni1395 Li, 2010, Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion, Science, 329, 85, 10.1126/science.1188063 Tanigaki, 2004, Regulation of αβ/γδ T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling, Immunity, 20, 611, 10.1016/S1074-7613(04)00109-8 Ciofani, 2006, Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation, Immunity, 25, 105, 10.1016/j.immuni.2006.05.010 Wojciechowski, 2007, E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression, J Immunol, 178, 5517, 10.4049/jimmunol.178.9.5717 Lauritsen, 2009, Marked induction of the helix-loop-helix protein Id3 promotes the γδ T cell fate and renders their functional maturation Notch independent, Immunity, 31, 565, 10.1016/j.immuni.2009.07.010 Ueda-Hayakawa, 2009, Id3 restricts the developmental potential of gammadelta lineage during thymopoiesis, J Immunol, 182, 5306, 10.4049/jimmunol.0804249 Ciofani, 2004, Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation, J Immunol, 172, 5230, 10.4049/jimmunol.172.9.5230 Maillard, 2006, The requirement for Notch signaling at the beta-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor, J Exp Med, 203, 2239, 10.1084/jem.20061020 Wang, 2006, The basic helix-loop-helix transcription factor HEBAlt is expressed in pro-T cells and enhances the generation of T cell precursors, J Immunol, 177, 109, 10.4049/jimmunol.177.1.109 Kleinman, 2008, Ikaros represses the transcriptional response to Notch signaling in T-cell development, Mol Cell Biol, 28, 7465, 10.1128/MCB.00715-08 Pajerowski, 2009, NKAP is a transcriptional repressor of Notch signaling and is required for T cell development, Immunity, 30, 696, 10.1016/j.immuni.2009.02.011 Xu, 2009, Pre-TCR-induced beta-catenin facilitates traversal through beta-selection, J Immunol, 182, 751, 10.4049/jimmunol.182.2.751 Xu, 2009, Sustained expression of pre-TCR induced beta-catenin in post-beta-selection thymocytes blocks T cell development, J Immunol, 182, 759, 10.4049/jimmunol.182.2.759 Pai, 2003, Critical roles for transcription factor GATA-3 in thymocyte development, Immunity, 19, 863, 10.1016/S1074-7613(03)00328-5 Bender, 2004, Critical functions for c-Myb at three checkpoints during thymocyte development, Nat Immunol, 5, 721, 10.1038/ni1085 McMillan, 2009, Promoter activity 5′ of Dβ2 is coordinated by E47, Runx1, and GATA-3, Mol Immunol, 46, 3009, 10.1016/j.molimm.2009.06.013 Robey, 1996, An activated form of Notch influences the choice between CD4 and CD8 T cell lineages, Cell, 87, 483, 10.1016/S0092-8674(00)81368-9 Fowlkes, 2002, A reassessment of the effect of activated Notch1 on CD4 and CD8 T cell development, J Immunol, 169, 1817, 10.4049/jimmunol.169.4.1817 Laky, 2005, Receptor signals and nuclear events in CD4 and CD8 T cell lineage commitment, Curr Opin Immunol, 17, 116, 10.1016/j.coi.2005.02.004 Yasutomo, 2000, The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate, Nature, 404, 506, 10.1038/35006664 Izon, 2001, Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength, Immunity, 14, 253, 10.1016/S1074-7613(01)00107-8 Laky, 2007, Presenilins regulate alphabeta T cell development by modulating TCR signaling, J Exp Med, 204, 2115, 10.1084/jem.20070550 Laky, 2006, TCR and Notch signaling in CD4 and CD8 T-cell development, Immunol Rev, 209, 274, 10.1111/j.0105-2896.2006.00358.x Laky, 2008, Notch signaling in CD4 and CD8 T cell development, Curr Opin Immunol, 20, 197, 10.1016/j.coi.2008.03.004 Singer, 2008, Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice, Nat Rev Immunol, 8, 788, 10.1038/nri2416 Muroi, 2008, Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate, Nat Immunol, 9, 1113, 10.1038/ni.1650 Wang, 2008, Dinstinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4+ T cells, Nat Immunol, 9, 1122, 10.1038/ni.1647 Yuan, 2010, C-myb promotes the survival of CD4+CD8+ double-positive thymocytes through upregulation of Bcl-XL, J Immunol, 184, 2793, 10.4049/jimmunol.0902846 Maurice, 2007, C-myb regulates lineage choice in developing thymocytes via its target gene GATA-3, EMBO, 26, 3629, 10.1038/sj.emboj.7601801 Aliahmad, 2008, Development of all CD4 T lineages requires nuclear factor TOX, J Exp Med, 205, 245, 10.1084/jem.20071944 Egawa, 2008, ThPOK acts late in specification of the helper T cell lineage and supresses Runx-mediated commitment to the cytotoxic T cell lineage, Nat Immunol, 9, 1131, 10.1038/ni.1652 Wang, 2009, CD4-CD8 lineage differentiation: Thpok-ing into the nucleus, J Immunol, 183, 2903, 10.4049/jimmunol.0901041 Setoguchi, 2008, Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development, Science, 319, 822, 10.1126/science.1151844 He, 2008, CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus, Immunity, 28, 346, 10.1016/j.immuni.2008.02.006 Zamisch, 2009, The transcription factor Ets1 is important for CD4 expression and Runx3 up-regulation during CD8 T cell differentiation in the thymus, J Exp Med, 206, 2685, 10.1084/jem.20092024 Sakaguchi, 2010, The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes, Nat Immunol, 11, 442, 10.1038/ni.1860 Hossain, 2008, ICAT expression disrupts beta-catenin-TCF interactions and impairs survival of thymocytes and activated mature T cells, Int Immunol, 20, 925, 10.1093/intimm/dxn051 Yu, 2007, Beta-catenin regulates positive selection of thymocytes but not lineage commitment, J Immunol, 178, 5028, 10.4049/jimmunol.178.8.5028 Weber, 2011, A critical role for TCF-1 in T-lineage specification and differentiation, Nature, 476, 63, 10.1038/nature10279