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Modulated expression of notch1 during thymocyte development
RP Hasserjian, JC Aster, F Davi, DS Weinberg and J Sklar
Department of Pathology, Brigham and Women's Hospital, Harvard Medical
School, Boston, MA 02115, USA.
The Notch gene family encodes transmembrane proteins that have been
implicated 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 T-cell differentiation. To investigate the
patterns of expression of NOTCH1 protein in thymocytes of the developing
and mature thymus, antibodies raised against NOTCH1 were used to perform
immunohistochemical and flow cytometric analyses. Strong staining for
NOTCH1 within the fetal murine thymus was observed as early as 13.5 days
postcoitum. By 17.5 days postcoitum, preferential staining of superficial
cortical thymocytes was observed, with weak staining of developing medulla.
Flow cytometric analysis and immunohistochemical staining of flow-sorted
cells confirmed that the highest levels of NOTCH1 expression in adult
murine thymus were present in immature cortical thymocytes (CD24high,
CD4-CD8-). In contrast, NOTCH1 expression 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 pattern of NOTCH1 expression during T-cell
differentiation and suggest that downregulation of NOTCH1 may be required
for maturation of cortical thymocytes.
Volume 88,
Issue 3,
pp. 970-976,
08/01/1996
Copyright © 1996 by The American Society of Hematology
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