Notch ligands Delta 1 and Jagged1 transmit distinct signals to T-cell precursors.
Signaling through the Notch pathway plays an essential role in inducing T-lineage commitment and promoting the maturation of immature thymocytes. Using an in vitro culture system, we show that 2 different classes of Notch ligands, Jagged1 or Delta1, transmit distinct signals to T-cell progenitors. OP9 stromal cells expressing either Jagged1 or Delta1 inhibit the differentiation of DN1 thymocytes into the B-cell lineage, but only the Delta1-expressing stromal cells promote the proliferation and maturation of T-cell progenitors through the early double-negative (DN) stages of thymocyte development. Whereas the majority of bone marrow-derived stem cells do not respond to Jagged1 signals, T-cell progenitors respond to Jagged1 signals during a brief window of their development between the DN1 and DN3 stages of thymic development. During these stages, Jagged1 signals can influence the differentiation of immature thymocytes along the natural killer (NK) and gamma delta T-cell lineages.
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Sophie M
SM
Lehar
James
J
Dooley
Andrew G
AG
Farr
Michael J
MJ
Bevan
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D006131:Growth Inhibitors / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000276:immunology*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism / Q000502:physiology
D002135:Calcium-Binding Proteins; D006131:Growth Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C064045:delta protein