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

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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.