Wnt9a Is Required for the Aortic Amplification of Nascent Hematopoietic Stem Cells.
All mature blood cell types in the adult animal arise from hematopoietic stem and progenitor cells (HSPCs). However, the developmental cues regulating HSPC ontogeny are incompletely understood. In particular, the details surrounding a requirement for Wnt/β-catenin signaling in the development of mature HSPCs are controversial and difficult to consolidate. Using zebrafish, we demonstrate that Wnt signaling is required to direct an amplification of HSPCs in the aorta. Wnt9a is specifically required for this process and cannot be replaced by Wnt9b or Wnt3a. This proliferative event occurs independently of initial HSPC fate specification, and the Wnt9a input is required prior to aorta formation. HSPC arterial amplification occurs prior to seeding of secondary hematopoietic tissues and proceeds, in part, through the cell cycle regulator myca (c-myc). Our results support a general paradigm, in which early signaling events, including Wnt, direct later HSPC developmental processes.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Stephanie
S
Grainger
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Biomedical Sciences Graduate Studies, University of California, San Diego, La Jolla, CA 92037, USA.
Jenna
J
Richter
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Raquel Espín
RE
Palazón
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Claire
C
Pouget
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Brianna
B
Lonquich
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Sara
S
Wirth
University of Münster, 48149 Münster, Germany.
Kathrin Sabine
KS
Grassme
University of Münster, 48149 Münster, Germany; Max-Planck-Institute for Molecular Biomedicine, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Münster, 48149 Münster, Germany.
Wiebke
W
Herzog
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Matthew R
MR
Swift
Section on Vertebrate Organogenesis, Division of Developmental Biology, NICHD, NIH, Bethesda, MD 20892, USA.
Brant M
BM
Weinstein
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: dtraver@ucsd.edu.
David
D
Traver
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: kwillert@ucsd.edu.
Karl
K
Willert
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000196:embryology*; D002452:Cell Count; D002453:Cell Cycle; D049109:Cell Proliferation; D055018:Hemangioblasts / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*
D051153:Wnt Proteins; C554086:Wnt9a protein, zebrafish; D029961:Zebrafish Proteins
HSCs; HSPCs; Myc; Wnt; Wnt9a; aorta; hematopoietic stem and progenitor cells; hematopoietic stem cells; proliferation