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

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.