title: Notch signaling is necessary for GATA3 function in the initiation of T cell development.
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.
authors.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
authors.forename: Katsuto
authors.initials: K
authors.lastname: Hozumi
authors.forename: Naoko
authors.initials: N
authors.lastname: Negishi
authors.forename: Izumi
authors.initials: I
authors.lastname: Tsuchiya
authors.forename: Natsumi
authors.initials: N
authors.lastname: Abe
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirano
authors.forename: Daisuke
authors.initials: D
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: James D
authors.initials: JD
authors.lastname: Engel
authors.forename: Sonoko
authors.initials: S
authors.lastname: Habu
mesh_terms: 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
chemical_list: D050990:GATA3 Transcription Factor; D051880:Receptors, Notch