Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 & Irf4 in zebrafish
- Huang, Y., Lu, Y., He, Y., Feng, Z., Zhan, Y., Huang, X., Liu, Q., Zhang, J., Li, H., Huang, H., Ma, M., Luo, L., Li, L.
- The Journal of biological chemistry 294(44): 16152-16163 (Journal)
- Registered Authors
- Huang, Honghui, Li, Li, Luo, Lingfei, Ma, Ming, Zhang, Jingjing
- development, lymphocyte, migration, transcription factor, zebrafish
- MeSH Terms
- Cell Differentiation/physiology
- Cell Proliferation
- Gene Regulatory Networks
- Hematopoietic Stem Cells/cytology
- Hematopoietic Stem Cells/metabolism
- Ikaros Transcription Factor/genetics
- Ikaros Transcription Factor/metabolism*
- Interferon Regulatory Factors/genetics
- Interferon Regulatory Factors/metabolism*
- Receptors, CCR/genetics
- Receptors, CCR/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- 31511326 Full text @ J. Biol. Chem.
Huang, Y., Lu, Y., He, Y., Feng, Z., Zhan, Y., Huang, X., Liu, Q., Zhang, J., Li, H., Huang, H., Ma, M., Luo, L., Li, L. (2019) Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 & Irf4 in zebrafish. The Journal of biological chemistry. 294(44):16152-16163.
Ikzf1 is a Krüppel-like zinc-finger transcription factor that plays indispensable roles in T and B cell development. Though the function of Ikzf1 has been extensively studied, the molecular mechanism underlying T lymphopoiesis remains incompletely defined during the embryonic stage. Here, we report that the genetic ablation of ikzf1 in mutant zebrafish resulted in abrogated embryonic T lymphopoiesis. This was ascribed to the impaired thymic migration, proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs). Ccr9a and Irf4a, two indispensable factors in T lymphopoiesis, were the direct targets of Ikzf1 and were absent in the ikzf1 mutants. Genetic deletion of either ccr9a or irf4a in the corresponding mutant embryos led to obvious T-cell development deficiency, which was mainly caused by the disrupted thymic migration of HSPCs. Restoration of ccr9a in ikzf1 mutants obviously promoted HSPC thymus-homing. However, the HSPCs then failed to differentiate into T cells. Additional replenishment of irf4a efficiently induced HSPC proliferation and T-cell differentiation. Our findings further demonstrate that ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4, and provide new insight into the genetic network of T lymphocyte development.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes