MODULATED EXPRESSION OF NOTCH1 DURING THYMOCYTE DEVELOPMENT

The Notch gene family encodes transmembrane proteins that have been im plicated in control of diverse cellular differentiation events in the fly, frog, and mouse, Mammalian Notch1 is expressed at high levels in thymus and is mutated in a subset of human T-cell acute lymphoblastic neoplasms, suggesting a role in if-cell differentiation, To investigat e the patterns of expression of NOTCH1 protein in thymocytes of the de veloping and mature thymus, antibodies raised against NOTCH1 were used to perform immunohistochemical and flow cytometric analyses. Strong s taining for NOTCH1 within the fetal murine thymus was observed as earl y as 13.5 days postcoitum. By 17.5 days postcoitum preferential staini ng of superficial cortical thymocytes was observed, with weak staining of developing medulla. Flow cytometric analysis and immunohistochemic al staining of flow-sorted cells confirmed that the highest levels of NOTCH1 expression in adult murine thymus were present in immature cort ical thymocytes (CD24high, CD4(-)CD8(-)). In contrast, NOTCH1 expressi on was low or absent in more mature cortical thymocytes (CD24low, CD4( +)CD8(+)), whereas intermediate levels of expression were observed in CD4(+)CD8(-) and CD4(-)CD8(+) cells. These data indicate a dynamic pat tern of NOTCH1 expression during T-cell differentiation and suggest th at downregulation of NOTCH1 may be required for maturation of cortical thymocytes. (C) 1996 by The American Society of Hematology.