Notch signaling is necessary for GATA3 function in the initiation of T cell development.
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.
Hozumi
Katsuto
K
Department of Immunology, and Research Center for Embryogenesis and Organogenesis, Tokai University School of Medicine, Isehara, Japan. hozumi@is.icc.u-tokai.ac.jp
Negishi
Naoko
N
Tsuchiya
Izumi
I
Abe
Natsumi
N
Hirano
Ken-ichi
K
Suzuki
Daisuke
D
Yamamoto
Masayuki
M
Engel
James D
JD
Habu
Sonoko
S
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques
D050990:GATA3 Transcription Factor; D051880:Receptors, Notch