Expression pattern of notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand-receptor interactions in intrathymic T cell development.
The suggested role of Notch1 or its mutants in thymocyte differentiation and T cell tumorigenesis raises the question of how the different members of the Notch family influence distinct steps in T cell development and the role played by Notch ligands in the thymus. We report here that different Notch receptor-ligand partnerships may occur inside the thymus, as we observed differential expression of Notch1, 2 and 3 receptors, their ligands Jagged1 and 2, and downstream intracellular effectors hairy and Enhancer of Split homolog 1 (HES-1) and hairy and Enhancer of Split homolog 5 (HES-5), depending on ontogenetic stage and thymic cell populations. Indeed, while Jagged2 is expressed in both stromal cells and thymocytes, Jagged1 expression is restricted to stromal cells. Moreover, a differential distribution of Notch3, with respect to Notch1, was observed in distinct age-related thymocyte subsets. Finally, Notch3 was preferentially up-regulated in thymocytes, following the induction of their differentiation by interaction with thymic epithelial cells expressing the cognate Jagged1 and 2 ligands, suggesting that, besides Notch1, Notch3 may also be involved in distinct steps of thymocyte development. Our results suggest that the Notch signaling pathway is involved in a complex interplay of T cell developmental stages, as a consequence of the heterogeneity and specific expression of members of the Notch receptor family and their cognate ligands, in distinct thymic cell compartments.
Felli
M P
MP
Department of Experimental Medicine, University of L'Aquila, Aquila 67100, Italy.
Maroder
M
M
Mitsiadis
T A
TA
Campese
A F
AF
Bellavia
D
D
Vacca
A
A
Mann
R S
RS
Frati
L
L
Lendahl
U
U
Gulino
A
A
Screpanti
I
I
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D008024:Ligands; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000096:biosynthesis; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000276:immunology; D017154:Stromal Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D008024:Ligands; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489734:Hes1 protein, mouse; C489685:Hes5 protein, mouse; C000606273:JAG1 protein, human; C490504:JAG2 protein, human; C000606274:Jag1 protein, mouse; C490503:Jag2 protein, mouse; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse; C499373:Notch3 protein, mouse; C073572:Notch4 protein, mouse; C077478:HES5 protein, human