Regulation of T lymphopoiesis by Notch1 and Lunatic fringe-mediated competition for intrathymic niches.
Notch1 activation regulates T lineage commitment and early T cell development. Fringe glycosyltransferases alter the sensitivity of Notch receptors to Delta-like versus Jagged Notch ligands, but their functions in T lymphopoiesis have not been defined. Here we show that developmental stage-specific expression of the glycosyltransferase lunatic fringe (Lfng) is required for coordination of the access of T cell progenitors to intrathymic niches that support Notch1-dependent phases of T cell development. Lfng-null progenitors generated few thymocytes in competitive assays, whereas Lfng overexpression converted thymocytes into 'supercompetitors' with enhanced binding of Delta-like ligands and blocked T lymphopoiesis from normal progenitors. We suggest that the ability of Lfng and Notch1 to control progenitor competition for limiting cortical niches is an important mechanism for the homeostatic regulation of thymus size.
Visan
Ioana
I
Program in Developmental Biology, Hospital for Sick Children Research Institute, and Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Tan
Joanne B
JB
Yuan
Julie S
JS
Harper
James A
JA
Koch
Ute
U
Guidos
Cynthia J
CJ
D000818:Animals; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D016695:Glycosyltransferases / Q000235:genetics / Q000502:physiology*; D007365:Intercellular Junctions / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D038041:Lymphopoiesis / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D051881:Receptor, Notch1 / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development*
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; D016695:Glycosyltransferases; C498392:Lfng protein, mouse