ZFIN ID: ZDB-PUB-190913-5
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.
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:
  • Animals
  • Cell Differentiation/physiology
  • Cell Proliferation
  • Gene Regulatory Networks
  • Hematopoiesis
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism
  • Ikaros Transcription Factor/genetics
  • Ikaros Transcription Factor/metabolism*
  • Interferon Regulatory Factors/genetics
  • Interferon Regulatory Factors/metabolism*
  • Lymphopoiesis/genetics
  • Lymphopoiesis/physiology*
  • Mutation
  • Receptors, CCR/genetics
  • Receptors, CCR/metabolism*
  • T-Lymphocytes/cytology
  • T-Lymphocytes/metabolism*
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
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.
ADDITIONAL INFORMATION