From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation

Authors

  • Tomonori Hosoya,

    1. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
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  • Ivan Maillard,

    1. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
    2. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
    3. Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
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  • James D. Engel

    1. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
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James D. Engel
109 Zina Pitcher Place, 3072 BSRB
Ann Arbor, MI 48109, USA
Tel.: +1 734 615 7509
Fax: +1 734 615 8500
e-mail: engel@umich.edu

Abstract

Summary:  GATA family transcription factors play multiple vital roles in hematopoiesis in many cell lineages, and in particular, T cells require GATA-3 for execution of several developmental steps. Transcriptional activation of the Gata3 gene is observed throughout T-cell development and differentiation in a stage-specific fashion. GATA-3 has been described as a master regulator of T-helper 2 (Th2) cell differentiation in mature CD4+ T cells. During T-cell development in the thymus, its roles in the CD4 versus CD8 lineage choice and at the β-selection checkpoint are the best characterized. In contrast, its importance prior to β-selection has been obscured both by the developmental heterogeneity of double negative (DN) 1 thymocytes and the paucity of early T-lineage progenitors (ETPs), a subpopulation of DN1 cells that contains the most immature thymic progenitors that retain potent T-lineage developmental potential. By examining multiple lines of in vivo evidence procured through the analysis of Gata3 mutant mice, we have recently demonstrated that GATA-3 is additionally required at the earliest stage of thymopoiesis for the development of the ETP population. Here, we review the characterized functions of GATA-3 at each stage of T-cell development and discuss hypothetical molecular pathways that mediate these functions.

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