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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2718-2726. Prepublished online as a Blood First Edition Paper on June 19, 2007; DOI 10.1182/blood-2006-04-016535. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2006-04-016535v1 110/7/2718    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Paffett-Lugassy, N. Articles by Zon, L. I. Search for Related Content PubMed PubMed Citation Articles by Paffett-Lugassy, N. Articles by Zon, L. I. Related Collections Hemostasis, Thrombosis, and Vascular Biology Red Cells Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Functional conservation of erythropoietin signaling in zebrafish Noëlle Paffett-Lugassy1, Nelson Hsia1, Paula G. Fraenkel1, Barry Paw2, Irene Leshinsky3, Bruce Barut1, Nathan Bahary4, Jaime Caro3, Robert Handin2, and Leonard I. Zon1 1 Stem Cell Program and Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute; 2 Department of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 3 Department of Medicine, Division of Hematology, Thomas Jefferson University, Jefferson Medical College, Philadelphia, PA; 4 Departments of Molecular Genetics & Biochemistry, and Medicine, Division of Oncology, University of Pittsburgh School of Medicine, PA Erythropoietin (Epo) and its cognate receptor (EpoR) are required for maintaining adequate levels of circulating erythrocytes during embryogenesis and adulthood. Here, we report the functional characterization of the zebrafish epo and epor genes. The expression of epo and epor was evaluated by quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization, revealing marked parallels between zebrafish and mammalian gene expression patterns. Examination of the hypochromic mutant, weissherbst, and adult hypoxia-treated hearts indicate that zebrafish epo expression is induced by anemia and hypoxia. Overexpression of epo mRNA resulted in severe polycythemia, characterized by a striking increase in the number of cells expressing scl, c-myb, gata1, ikaros, epor, and ße1-globin, suggesting that both the erythroid progenitor and mature erythrocyte compartments respond to epo. Morpholino-mediated knockdown of the epor caused a slight decrease in primitive and complete block of definitive erythropoiesis. Abrogation of STAT5 blocked the erythropoietic expansion by epo mRNA, consistent with a requirement for STAT5 in epo signaling. Together, the characterization of zebrafish epo and epor demonstrates the conservation of an ancient program that ensures proper red blood cell numbers during normal homeostasis and under hypoxic conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: EPOR signaling: 450 million years' history Ji Zhang and Paul A. Ney Blood 2007 110: 2225-2226. [Full Text] [PDF] This article has been cited by other articles: P. Sathyanarayana, A. Dev, J. Fang, E. Houde, O. Bogacheva, O. Bogachev, M. Menon, S. Browne, A. Pradeep, C. Emerson, et al. EPO receptor circuits for primary erythroblast survival Blood, June 1, 2008; 111(11): 5390 - 5399. [Abstract] [Full Text] [PDF] D. Carradice and G. J. Lieschke Zebrafish in hematology: sushi or science? Blood, April 1, 2008; 111(7): 3331 - 3342. [Abstract] [Full Text] [PDF]

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