This is an archive of papers published by the staff and faculty of Fox Chase Cancer Center. For questions about content, please contact Talbot Research Library
Last updated on
Michie AM , Chan AC , Ciofani M , Carleton M , Lefebvre JM , He YP , Allman DM , Wiest DL , Zuniga-Pflucker JC , Izon DJ
Constitutive Notch signalling promotes CD4(-)CD8(-) thymocyte differentiation in the absence of the pre-TCR complex, by mimicking pre-TCR signals
International Immunology. 2007 Dec;19(12) :1421-1430
AbstractNotch1 signalling is essential for the commitment of multipotent lymphocyte precursors towards the alpha beta T-cell lineage and plays an important role in regulating beta-selection in CD4(-)CD8(-) double-negative (DN) thymocytes. However, the role played by Notch in promoting the development of CD4(+)CD8(+) double-positive (DP) thymocytes is poorly characterized. Here, we demonstrate that the introduction of a constitutively active Notch1 (ICN1) construct into RAG(-/-) lymphocyte precursors resulted in the generation of DP thymocytes in in vitro T-cell culture systems. Notably, developmental rescue was dependent not only on the presence of an intact Notch1 RAM domain but also on Delta-like signals, as ICN1-induced DP development in RAG(-/-) thymocytes occurred within an intact thymus or in OP9-DL1 co-cultures, but not in OP9-control co-cultures. Interestingly, ICN1 expression in SLP-76(-/-) precursors resulted in only a minimal developmental rescue to the immature CD8(+)!
NotesMichie, Alison M. Chan, Angela C. Ciofani, Maria Carleton, Michael Lefebvre, Juliette M. He, Yiping Allman, David M. Wiest, David L. Zuniga-Pfluecker, Juan Carlos Izon, David J. OXFORD UNIV PRESS