| First Author | French MB | Year | 2002 |
| Journal | J Immunol | Volume | 168 |
| Issue | 7 | Pages | 3173-80 |
| PubMed ID | 11907069 | Mgi Jnum | J:75586 |
| Mgi Id | MGI:2177094 | Doi | 10.4049/jimmunol.168.7.3173 |
| Citation | French MB, et al. (2002) Transgenic expression of numb inhibits notch signaling in immature thymocytes but does not alter T cell fate specification. J Immunol 168(7):3173-80 |
| abstractText | 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 gammadelta/alphabeta or CD4/CD8 T cell fate specification. |
