title: Distinct regulatory networks control the development of macrophages of different origins in zebrafish.
abstract: 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 use 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 and aorta-gonad-mesonephros for myelopoiesis, to address this issue. We show that RBI- and VDA-born macrophages are orchestrated by distinctive regulatory networks formed by the E-twenty-six (Ets) transcription factors Pu.1 and Spi-b, the zebrafish ortholog of mouse spleen focus forming virus proviral integration oncogene B (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 induction by Pu.1, partially compensates the function of Pu.1. In contrast, Pu.1 and Spi-b act in parallel and cooperatively to regulate the development of VDA-derived macrophages. Interestingly, these two distinct regulatory networks orchestrate the RBI- and VDA-born macrophage development largely by 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.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Guo
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.|Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, Institute of Genetic Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, State Key Laboratory Breeding Base of Eco-Environments and Bio-Resources of the Three Gorges Area, School of Life Science, Southwest University, Chongqing, People's Republic of China; and.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.|Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University, The Hong Kong University of Science and Technology Medical Center, Guangdong, Shenzhen, People's Republic of China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Wen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000254:growth & development / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006801:Humans; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008650:Mesonephros / Q000166:cytology / Q000254:growth & development / Q000276:immunology; D051379:Mice; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D015017:Yolk Sac / Q000166:cytology / Q000254:growth & development / Q000276:immunology; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D050835:Interferon Regulatory Factors; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1; C514177:Spi-B protein, mouse