title: Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo.
abstract: The adult blood system is established by hematopoietic stem cells (HSCs), which arise during development from an endothelial-to-hematopoietic transition of cells comprising the floor of the dorsal aorta. Expression of aortic runx1 has served as an early marker of HSC commitment in the zebrafish embryo, but recent studies have suggested that HSC specification begins during the convergence of posterior lateral plate mesoderm (PLM), well before aorta formation and runx1 transcription. Further understanding of the earliest stages of HSC specification necessitates an earlier marker of hemogenic endothelium. Studies in mice have suggested that GATA2 might function at early stages within hemogenic endothelium. Two orthologs of Gata2 exist in zebrafish: gata2a and gata2b. Here, we report that gata2b expression initiates during the convergence of PLM, becoming restricted to emerging HSCs. We observe Notch-dependent gata2b expression within the hemogenic subcompartment of the dorsal aorta that is in turn required to initiate runx1 expression. Our results indicate that Gata2b functions within hemogenic endothelium from an early stage, whereas Gata2a functions more broadly throughout the vascular system.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Emerald
authors.initials: E
authors.lastname: Butko
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Distel
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Pouget
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Bart
authors.initials: B
authors.lastname: Weijts
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Isao
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ng
authors.affiliation: Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Mosimann
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Fabienne E
authors.initials: FE
authors.lastname: Poulain
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: McPherson
authors.affiliation: University of Massachusetts at Worcester, Worcester, MA 01605, USA.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Ni
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Stachura
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Del Cid
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Espín-Palazón
authors.affiliation: University of Massachusetts at Worcester, Worcester, MA 01605, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Lawson
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Dorsky
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA Department of Hematology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Wilson K
authors.initials: WK
authors.lastname: Clements
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA Section of Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093, USA dtraver@ucsd.edu.
authors.forename: David
authors.initials: D
authors.lastname: Traver
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology; D001426:Bacterial Proteins; D019521:Body Patterning / Q000502:physiology*; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055018:Hemangioblasts / Q000502:physiology*; D017403:In Situ Hybridization; D008164:Luminescent Proteins; D008648:Mesoderm / Q000196:embryology; D016376:Oligonucleotides, Antisense / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D001426:Bacterial Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D050989:GATA2 Transcription Factor; D008164:Luminescent Proteins; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; D000097573:Red Fluorescent Protein; C000597690:Gata2b protein, zebrafish; C472526:runx1 protein, zebrafish; C054562:yellow fluorescent protein, Bacteria
keywords: Gata2; Hematopoietic stem cell; Hemogenic endothelium; Notch; Subfunctionalization