Distinct regulatory networks control the development of macrophages of different origins in zebrafish

Yu, T., Guo, W., Tian, Y., Xu, J., Chen, J., Li, L., Wen, Z.
Blood   129(4): 509-519 (Journal)
Registered Authors
Li, Li, Wen, Zilong
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Aorta/cytology
  • Aorta/growth & development
  • Aorta/immunology
  • Cell Differentiation
  • Cell Lineage/genetics
  • Cell Lineage/immunology*
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • Humans
  • Immunity, Innate
  • Interferon Regulatory Factors/genetics
  • Interferon Regulatory Factors/immunology
  • Macrophages/cytology
  • Macrophages/immunology*
  • Mesonephros/cytology
  • Mesonephros/growth & development
  • Mesonephros/immunology
  • Mice
  • Organ Specificity
  • Protein Isoforms/genetics
  • Protein Isoforms/immunology
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/immunology*
  • Proto-Oncogene Proteins c-ets/genetics
  • Proto-Oncogene Proteins c-ets/immunology
  • Signal Transduction
  • Trans-Activators/genetics
  • Trans-Activators/immunology*
  • Yolk Sac/cytology
  • Yolk Sac/growth & development
  • Yolk Sac/immunology
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/immunology*
27940477 Full text @ Blood
Macrophages are key components of the innate immune system and play pivotal roles in immune response, organ development and tissue homeostasis. Studies in mice and zebrafish have shown that tissue-resident macrophages derived from different hematopoietic origins manifest distinct developmental kinetics and colonization potential. Yet, the genetic programs controlling the development of macrophages of different origins remain incompletely defined. In this study, we utilize zebrafish, where tissue-resident macrophages arise from the rostral blood island (RBI) and ventral wall of dorsal aorta (VDA), the zebrafish hematopoietic tissue equivalents to the mouse yolk sac (YS) and aorta-gonad-mesonephros (AGM) for myelopoiesis, to address this issue. We show that RBI- and VDA-born macrophages are orchestrated by distinctive regulatory networks formed by the Ets transcription factors Pu.1 and Spi-b, the zebrafish orthologue of mouse SPI-B, and the helix-turn-helix DNA-binding domain containing protein Irf8. Epistatic studies document that during RBI macrophage development, Pu.1 acts upstream of Spi-b, which, upon induced by Pu.1, partially compensates the function of Pu.1. In contrast, Pu.1 and Spi-b act in parallel and co-operatively to regulate the development of VDA-derived macrophages. Interestingly, these two distinct regulatory networks orchestrate the RBI- and VDA-born macrophage development largely through regulating a common downstream gene Irf8. Our study indicates that macrophages derived from different origins are governed by distinct genetic networks formed by the same repertoire of myeloid-specific transcription factors.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes