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Notch signaling is necessary for GATA3 function in the initiation of T cell development
Authors:Hozumi Katsuto  Negishi Naoko  Tsuchiya Izumi  Abe Natsumi  Hirano Ken-ichi  Suzuki Daisuke  Yamamoto Masayuki  Engel James D  Habu Sonoko
Affiliation:Department of Immunology, and Research Center for Embryogenesis and Organogenesis, Tokai University School of Medicine, Isehara, Japan. hozumi@is.icc.u-tokai.ac.jp
Abstract:
GATA3 and Notch1 are essential for T cell development at the earliest stage, but their mutual roles in this process remain to be clarified. In this study, we demonstrated that impairment of T lymphopoiesis in hematopoietic progenitor cells (HPC) of GATA3-deficient fetal liver (FL) on day 11.5 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 T cell fate specification but is not sufficient without GATA3. On the other hand, Notch signaling is sufficient for blockage of B cell development without GATA3, suggesting that T cell fate specification at the branching point does not result simply from the developmental arrest of B cell lineage by Notch signaling.
Keywords:GATA3  Notch signaling  Thymopoiesis
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