The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division.
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.
Aguado
Rocio
R
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Parque Tecnológico Ciencias de Salud, Granada, Spain.
Martin-Blanco
Nadia
N
Caraballo
Michael
M
Canelles
Matilde
M
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D049109:Cell Proliferation; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism; D005434:Flow Cytometry; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000378:metabolism*
D053645:Interleukin-2 Receptor alpha Subunit; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch; D050721:Proto-Oncogene Proteins c-cbl; C493849:Cbl protein, mouse