PUBLICATION

Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 & Irf4 in zebrafish

Authors
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.
ID
ZDB-PUB-190913-5
Date
2019
Source
The Journal of biological chemistry   294(44): 16152-16163 (Journal)
Registered Authors
Huang, Honghui, Li, Li, Luo, Lingfei, Ma, Ming, Zhang, Jingjing
Keywords
development, lymphocyte, migration, transcription factor, zebrafish
MeSH Terms
  • Mutation
  • Cell Proliferation
  • Interferon Regulatory Factors/genetics
  • Interferon Regulatory Factors/metabolism*
  • Gene Regulatory Networks
  • Zebrafish/embryology*
  • T-Lymphocytes/cytology
  • T-Lymphocytes/metabolism*
  • Cell Differentiation/physiology
  • Ikaros Transcription Factor/genetics
  • Ikaros Transcription Factor/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism
  • Animals
  • Hematopoiesis
  • Receptors, CCR/genetics
  • Receptors, CCR/metabolism*
  • Lymphopoiesis/genetics
  • Lymphopoiesis/physiology*
(all 21)
PubMed
31511326 Full text @ J. Biol. Chem.
Abstract
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.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
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Engineered Foreign Genes
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Citation
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.