Role of GATA-3 During CD4/CD8 Lineage Commitment

描述（由申请人提供）：在这项拨款中，我们提出了一些旨在详细了解转录因子GATA-3在胸腺CD4/CD8谱系承诺中的作用的实验。我们最近的研究表明，GATA-3在发育成CD4谱系的未成熟胸腺细胞中存在差异表达，并且通过改变胸腺中GATA-3的活性，我们可以影响谱系承诺。我们现在将：

DESCRIPTION (provided by applicant): In this grant we propose a number of experiments aimed at understanding in detail the role of the transcription factor GATA-3 during CD4/CD8 lineage commitment in the thymus. We have recently shown that GATA-3 is differentially expressed in immature thymocytes that develop into the CD4 lineage, and that by modifying GATA-3 activity in the thymus we can bias lineage commitment. We will now: Dissect the mechanisms that regulate TCR-induced GATA-3 upregulation in the thymus, using a gain-of function/loss-of-function genetic approach to identify the signal transduction pathways involved in this process in normal DP thymocytes. Use reaggregate fetal thymic organ culture (rFTOC), lentiviral transgenesis and different GATA-3 mutants to map the structural regions of GATA-3 required for its effect during CD4/CD8 lineage commitment. Analyze the interactions of GATA-3 with two transcription factors, Egr-2 and Lmo-4, that we have identified as preferentially expressed in CD4 lineage intermediates in a genome-wide screen. These studies should provide us with a better understanding of the mechanisms that control CD4/CD8 lineage commitment, and, more widely, will provide clues about the genetic networks that establish cell fate determination and developmental programs in the thymus.