Subversion of the T/B lineage decision in the thymus by lunatic fringe-mediated inhibition of Notch-1.
Notch-1 signaling is essential for lymphoid progenitors to undergo T cell commitment, but the mechanism has not been defined. Here we show that thymocytes ectopically expressing Lunatic Fringe, a modifier of Notch-1 signaling, induce lymphoid progenitors to develop into B cells in the thymus. This cell fate switch resulted from Lunatic Fringe-mediated inhibition of Notch-1 function, as revealed by experiments utilizing lymphoid progenitors in which Notch-1 activity was genetically manipulated. These data identify Lunatic Fringe as a potent regulator of Notch-1 during the T/B lineage decision and show that an important function of Notch-1 in T cell commitment is to suppress B cell development in the thymus.
Koch
U
U
Program in Developmental Biology, Hospital for Sick Children Research Institute, Toronto, Canada.
Lacombe
T A
TA
Holland
D
D
Bowman
J L
JL
Cohen
B L
BL
Egan
S E
SE
Guidos
C J
CJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D019070:Cell Lineage; D016695:Glycosyltransferases; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors
D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014157:Transcription Factors; D016695:Glycosyltransferases; C498392:Lfng protein, mouse