title: Ectopic expression of Hoxb4a in hemangioblasts promotes hematopoietic development in early embryogenesis of zebrafish.
abstract: Hemangioblast, including primitive hematopoietic progenitor cells, play an important role in hematopoietic development, however, the underlying mechanism for the propagation of hematopoietic progenitor cells remains elusive. A variety of regulatory molecules activated in early embryonic development play a critical role in the maintenance of function of hematopoietic progenitor cells. Homeobox transcription factors are an important class of early embryonic developmental regulators determining hematopoietic development. However, the effect of homeobox protein Hox-B4 (HOXB4) ectopic expression on the development of hemangioblasts has not been fully addressed. This study aimed to investigate the role of Hoxb4a, an ortholog gene of HOXB4 in zebrafish, in the hematopoietic development in zebrafish. A transgenic zebrafish line was established with Cre-loxP system that stably overexpressed enhanced green fluorescent protein (EGFP)-tagged Hoxb4a protein under the control of hemangioblast-specific lmo2 promoter. Overexpression of Hoxb4a in the development of hemangioblasts resulted in a considerable increase in the number of stem cell leukemia (scl) and lmo2-positive primitive hematopoietic progenitor cells occurring in the posterior intermediate cell mass (ICM). Interestingly, Hoxb4a overexpression also disrupted the development of myelomonocytes in the anterior yolk sac and the posterior ICM, without affecting erythropoiesis in the posterior ICM. Taken together, these results indicate that Hoxb4a favours the development of hematopoietic progenitor cells originated from hemangioblasts in vivo.
authors.affiliation: Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Centre & Sino-US Joint Laboratory for Medical Sciences, Laboratory Animal Centre, Guiyang Medical University, Guiyang, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Shu
authors.affiliation: Laboratory of Development and Diseases and Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Hematology (SIH), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhou
authors.affiliation: Laboratory of Development and Diseases and Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Hematology (SIH), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Laboratory of Development and Diseases and Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Hematology (SIH), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.affiliation: Laboratory of Development and Diseases and Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Hematology (SIH), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.affiliation: Laboratory of Development and Diseases and Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Hematology (SIH), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory of Development and Diseases and Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Hematology (SIH), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Fu
authors.affiliation: Laboratory of Development and Diseases and Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Hematology (SIH), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Centre & Sino-US Joint Laboratory for Medical Sciences, Laboratory Animal Centre, Guiyang Medical University, Guiyang, China.|Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
authors.affiliation: Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Centre & Sino-US Joint Laboratory for Medical Sciences, Laboratory Animal Centre, Guiyang Medical University, Guiyang, China.
authors.forename: Zhi-Xu
authors.initials: ZX
authors.lastname: He
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D000066630:Ectopic Gene Expression; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055018:Hemangioblasts / Q000378:metabolism*; D006410:Hematopoiesis / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D060588:LIM Domain Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C514262:Hoxb4a protein, zebrafish; D060588:LIM Domain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C513186:lmo2 protein, zebrafish
keywords: Hoxb4a; hemangioblast; hematopoietic progenitor cells; zebrafish embryos