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Arthur and Sonia Labatt Brain Tumor Research Center and
Program in Developmental Biology, Hospital for Sick Children, Toronto, Ontario, Canada
The conserved adaptor protein Numb is an intrinsic cell fate
determinant that functions by antagonizing Notch-mediated signal
transduction. The Notch family of membrane receptors controls cell
survival and cell fate determination in a variety of organ systems and
species. Recent studies have identified a role for mammalian Notch-1
signals at multiple stages of T lymphocyte development. We have
examined the role of mammalian Numb (mNumb) as a Notch regulator and
cell fate determinant during T cell development. Transgenic
overexpression of mNumb under the control of the Lck
proximal promoter reduced expression of several Notch-1 target genes,
indicating that mNumb antagonizes Notch-1 signaling in vivo. However,
thymocyte development, cell cycle, and survival were unperturbed by
mNumb overexpression, even though transgenic Numb was expressed at an
early stage in thymocyte development
(CD4-CD8-CD3- cells that were
CD44+CD25+ or
CD44-CD25+; double-negative 2/3). Moreover,
bone marrow from mNumb transgenic mice showed no defects in
thymopoiesis in competitive repopulation experiments. Our results
suggest that mNumb functions as a Notch-1 antagonist in immature
thymocytes, but that suppression of Notch-1 signaling at this stage
does not alter 
/
or CD4/CD8 T cell fate
specification.
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