Pre-thymic Notch signaling is necessary for GATA3 function in the initiation of T cell development.

GATA3和Notch1对T细胞的早期命运是必不可少的，但它们在这一过程中的相互作用仍有待阐明。在这项研究中，我们证明了GATA3基因缺陷胎肝(E11.5天)造血祖细胞T淋巴细胞增殖的损伤仅通过GATA3和Notch1细胞内区的共同作用而不是单独使用。然而，GATA3的引入只足以在晚期GATA3缺陷的FL细胞中诱导T细胞，那里的Notch信号是可以很好地检测到的。这表明Notch信号对GATA3起作用是必需的，但如果没有GATA3，Notch信号是不够的。另一方面，Notch信号足以在没有GATA3的情况下阻断B细胞的发育，这表明指定分支点的T细胞命运并不是简单地通过Notch信号阻止B细胞谱系的发育。

GATA3 and Notch1 are essential for T cell fate at the earliest stage, but their mutual roles in this process remain to be clarified. In this study, we demonstrated that the impairment of T lymphopolesis in hematopoietic progenitor cells of GATA3-deficient fetal liver (FL) on 11.5 days of gestation (E11.5) was rescued only by introduction of both GATA3 and the intracellular region of Notch1 but not by either alone. However, the introduction of GATA3 only was sufficient for T cell induction in GATA3-deficient FL cells at the advanced stage, where Notch signaling is well detectable. This indicates that Notch signaling is necessary for GATA3 to function for the specification of T cell fate but is not sufficient without GATA3. On the other hand, Notch signaling is enough for the blockage of B cell development without GATA3, suggesting that specification of T cell fate at the branching point does not result simply from the developmental arrest of B cell lineage by Notch signaling.