title: Distinct regulation of the anterior and posterior myeloperoxidase expression by Etv2 and Gata1 during primitive Granulopoiesis in zebrafish.
abstract: Neutrophilic granulocytes are the most abundant type of myeloid cells and form an essential part of the innate immune system. In vertebrates the first neutrophils are thought to originate during primitive hematopoiesis, which precedes hematopoietic stem cell formation. In zebrafish embryos, it has been suggested that primitive neutrophils may originate in two distinct sites, the anterior (ALPM) and posterior lateral plate mesoderm (PLPM). An ETS-family transcription factor Etsrp/Etv2/ER71 has been implicated in vasculogenesis and hematopoiesis in multiple vertebrates. However, its role during neutrophil development is not well understood. Here we demonstrate using zebrafish embryos that Etv2 has a specific cell-autonomous function during primitive neutropoiesis in the anterior lateral plate mesoderm (ALPM) but has little effect on erythropoiesis or the posterior lateral plate mesoderm (PLPM) expression of neutrophil marker myeloperoxidase mpo/mpx. Our results argue that ALPM-derived neutrophils originate from etv2-expressing cells which downregulate etv2 during neutropoiesis. We further show that Scl functions downstream of Etv2 in anterior neutropoiesis. Additionally, we demonstrate that mpx expression within the PLPM overlaps with gata1 expression, potentially marking the cells with a dual myelo-erythroid potential. Intriguingly, initiation of mpx expression in the PLPM is dependent on gata1 but not etv2 function. Our results demonstrate that mpx expression is controlled differently in the ALPM and PLPM regions and describe novel roles for etv2 and gata1 during primitive neutropoiesis.
authors: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
authors: Nicole O
authors: NO
authors: Glenn
authors: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
authors: Jennifer A
authors: JA
authors: Schumacher
authors: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
authors: Hyon J
authors: HJ
authors: Kim
authors: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
authors: Emma J
authors: EJ
authors: Zhao
authors: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
authors: Jurate
authors: J
authors: Skerniskyte
authors: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
authors: Saulius
authors: S
authors: Sumanas
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D004625:Embryo, Nonmammalian; D050982:GATA1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D019891:Leukopoiesis; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D060172:Morpholinos / Q000235:genetics; D009504:Neutrophils / Q000166:cytology*; D009195:Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D020107:Troponin T / Q000235:genetics; D015027:Zebrafish / Q000097:blood / Q000196:embryology*; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050982:GATA1 Transcription Factor; D060172:Morpholinos; D009195:Peroxidase; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015534:Trans-Activators; D020107:Troponin T; D029961:Zebrafish Proteins; D000099232:Proto-Oncogene Protein Spi-1; C509408:Etv2 protein, zebrafish; C494691:gata1a protein, zebrafish; C489367:tal1 protein, zebrafish; C480681:tnnt2a protein, zebrafish
keywords: Er71; Etsrp; Etv2; Gata1; Granulocytes; Myeloid; Neutrophil; Primitive hematopoiesis; Zebrafish