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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1824-1830. Prepublished online as a Blood First Edition Paper on June 1, 2007; DOI 10.1182/blood-2007-03-078287. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-03-078287v1 110/6/1824    most recent Alert me when this article is cited Alert me if a correction is posted 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 Ma, A. C.H. Articles by Leung, A. Y.H. Search for Related Content PubMed PubMed Citation Articles by Ma, A. C.H. Articles by Leung, A. Y.H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 6, 2007 Accepted May 23, 2007 The role of jak2a in zebrafish hematopoiesis Alvin C.H. Ma, Alister C. Ward, Raymond Liang, and Anskar Y.H. Leung* Department of Medicine, University of Hong Kong, Hong Kong, China School of Medicine, Deakin University, Geelong, Victoria, Australia * Corresponding author; email: ayhleung{at}hku.hk. Janus kinase 2 (Jak2) transduces signals from hematopoietic cytokines and a gain-of-function mutation (Jak2V617F) is associated with myeloproliferative diseases particularly polycythemia vera. In this study, we examined the role of jak2a in zebrafish embryos in knock-down and over-expression studies using morpholinos (MOs) targeting the 5'untranslated region (UTR) (jak2aUTR-MO) and splice-site junction (jak2aSS-MO) of jak2a, a Jak inhibitor AG490 and a constitutive-active form of jak2a (jak2aca). At 18 and 24 hours-post-fertilization (hpf), jak2a is expressed predominantly in the intermediate cell mass (ICM, site of primitive hematopoiesis) of wild-type and chordin morphant embryos (characterized by expansion of ICM). Both jak2a MOs and AG490 reduced gata1+ (erythroid) cells in Tg(gata1:GFP) embryos, stat5 phosphorylation and gene expression associated with early progenitors (scl and lmo2), erythroid (gata1, he1 and he1) and myeloid [spi1 (early) and mpo (late)] lineages. The chordin morphant is associated with increased stat5 phosphorylation and both jak2a MOs and treatment with AG490 significantly ameliorated ICM expansion and hematopoietic gene up-regulation in these embryos. Injection of plasmid encoding jak2aca significantly increased erythropoiesis and expression of gata1, he1 and he1, spi1, mpo and l-plastin. In conclusion, zebrafish jak2a is involved in primitive hematopoiesis under normal and deregulated conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Liongue, C. J. Hall, B. A. O'Connell, P. Crosier, and A. C. Ward Zebrafish granulocyte colony-stimulating factor receptor signaling promotes myelopoiesis and myeloid cell migration Blood, March 12, 2009; 113(11): 2535 - 2546. [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] J. A. Martinez-Agosto, H. K.A. Mikkola, V. Hartenstein, and U. Banerjee The hematopoietic stem cell and its niche: a comparative view Genes & Dev., December 1, 2007; 21(23): 3044 - 3060. [Abstract] [Full Text] [PDF]

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