| First Author | Dose M | Year | 2006 |
| Journal | Blood | Volume | 108 |
| Issue | 8 | Pages | 2669-77 |
| PubMed ID | 16788099 | Mgi Jnum | J:139467 |
| Mgi Id | MGI:3808099 | Doi | 10.1182/blood-2006-02-005900 |
| Citation | Dose M, et al. (2006) c-Myc mediates pre-TCR-induced proliferation but not developmental progression. Blood 108(8):2669-77 |
| abstractText | Constitutive and cell-autonomous signals emanating from the pre-T-cell receptor (pre-TCR) promote proliferation, survival and differentiation of immature thymocytes. We show here that induction of pre-TCR signaling resulted in rapid elevation of c-Myc protein levels. Cre-mediated thymocyte-specific ablation of c-Myc in CD25(+)CD44(-) thymocytes reduced proliferation and cell growth at the pre-TCR checkpoint, resulting in thymic hypocellularity and a severe reduction in CD4(+)CD8(+) thymocytes. In contrast, c-Myc deficiency did not inhibit pre-TCR-mediated differentiation or survival. Myc(-/-) double-negative (DN) 3 cells progressed to the double-positive (DP) stage and up-regulated TCRalphabeta surface expression in the absence of cell proliferation, in vivo as well as in vitro. These observations indicate that distinct signals downstream of the pre-TCR are responsible for proliferation versus differentiation, and demonstrate that c-Myc is only required for pre-TCR-induced proliferation but is dispensable for developmental progression from the DN to the DP stage. |
