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Publication : The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division.

First Author  Aguado R Year  2010
Journal  Blood Volume  116
Issue  10 Pages  1705-14
PubMed ID  20530794 Mgi Jnum  J:164517
Mgi Id  MGI:4834079 Doi  10.1182/blood-2009-10-246777
Citation  Aguado R, et al. (2010) The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division. Blood 116(10):1705-14
abstractText  Stem cells must proliferate and differentiate to generate the lineages that shape mature organs; understanding these 2 processes and their interaction is one of the central themes in current biomedicine. An intriguing aspect is asymmetric division, by which 2 daughter cells with different fates are generated. Several cell fate determinants participate in asymmetric division, with the endocytic adaptor Numb as the best-known example. Here, we have explored the role of asymmetric division in thymocyte development, visualizing the differential segregation of Numb and pre-TCR in thymic precursors. Analysis of mice where Numb had been inhibited by expressing a dominant negative revealed enhanced pre-T-cell receptor (TCR) signaling and a smaller thymus. Conversely, Numb overexpression resulted in loss of asymmetric division and a larger thymus. The conclusion is that Numb determines the levels of pre-TCR signaling in dividing thymocytes and, ultimately, the size of the pool from which mature T lymphocytes are selected.
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