From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation.
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.
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Tomonori
T
Hosoya
Ivan
I
Maillard
James D
JD
Engel
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology*; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D018448:Models, Immunological; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000254:growth & development / Q000276:immunology*
D050990:GATA3 Transcription Factor