ABSTRACT
T lymphocytes are key cellular components of an acquired immune system and play essential roles in cell-mediated immunity. T cell development occurs in the thymus where 95% of immature thymocytes are eliminated via apoptosis. It is known that mutation of Zeb1, one of the retinoblastoma 1 (Rb1) target genes, results in a decrease in the number of immature T cells in mice. E2F1, an RB1-interacting protein, has been shown to regulate mature T cell development by interfering with thymocyte apoptosis. However, whether Rb1 regulates thymocyte development in vivo still needs to be further investigated. Here, we use a zebrafish model to investigate the role of Rb1 in T cell development. We show that Rb1-deficient fish exhibit a significant reduction in T cell number during early development that it is attributed to the accelerated apoptosis of immature T cells in a caspase-dependent manner. We further show that E2F1 overexpression could mimic the reduced T lymphocytes phenotype of Rb1 mutants, and E2F1 knockdown could rescue the phenotype in Rb1-deficient mutants. Collectively, our data indicate that the Rb1-E2F1-caspase axis is crucial for protecting immature T cells from apoptosis during early T lymphocyte maturation.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: Z.Z., W.Z., Y.Z.; Methodology: Z.Z., W.L., L.Z., Z.H., X.C., N.M., Y.Z.; Software: Z.Z., W.L., L.Z., X.C.; Validation: Z.Z., W.L., L.Z., Y.Z.; Formal analysis: Z.Z., W.L., L.Z., Z.H., N.M., J.X., W.Z., Y.Z.; Investigation: Z.Z., W.L., L.Z.; Resources: Z.Z., X.C., Y.Z.; Data curation: Z.Z., L.Z., Z.H., N.M., J.X., W.Z., Y.Z.; Writing - original draft: Z.Z., Y.Z.; Writing - review & editing: W.L., Z.H., J.X., W.Z., Y.Z.; Visualization: Z.Z., X.C., W.Z., Y.Z.; Supervision: W.Z., Y.Z.; Project administration: W.Z., Y.Z.; Funding acquisition: W.L., W.Z., Y.Z.
Funding
This work was supported by the National Natural Science Foundation of China (31701264), the Ministry of Science and Technology of the People's Republic of China (Project 863, SS2015AA020309) and the Team Program of the Guangdong Natural Science Foundation (2014A030312002).
Supplementary information
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.158139.supplemental
- Received August 13, 2017.
- Accepted December 1, 2017.
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