BMP signaling modulates Hepcidin expression in zebrafish embryos independent of Hemojuvelin Gibert, Yann, Lattanzi, Victoria J., Zhen, Aileen W., Vedder, Lea, Brunet, Frederic, Fasse, Sarah A., Babitt, Jodie L., Lin, Herbert Y., Hammerschmidt, Matthias and Fraenkel, Paula G. 2011, BMP signaling modulates Hepcidin expression in zebrafish embryos independent of Hemojuvelin, PLoS one, vol. 6, no. 1, pp. 1-14, doi: 10.1371/journal.pone.0014553. Attached Files Name Description MIMEType Size Downloads gibert-bmpsignaling-2011.pdf Published version application/pdf 3.66MB 3 Title BMP signaling modulates Hepcidin expression in zebrafish embryos independent of Hemojuvelin Formatted title BMP signaling modulates Hepcidin expression in zebrafish embryos independent of Hemojuvelin Author(s) Gibert, Yann Lattanzi, Victoria J. Zhen, Aileen W. Vedder, Lea Brunet, Frederic Fasse, Sarah A. Babitt, Jodie L. Lin, Herbert Y. Hammerschmidt, Matthias Fraenkel, Paula G. Journal name PLoS one Volume number 6 Issue number 1 Article ID e14553 Start page 1 End page 14 Total pages 14 Publisher Public Library of Science Place of publication San Francisco, California Publication date 2011-01 ISSN 1932-6203 Keyword(s) hemojuvelin (Hjv) hepcidin expression bone morphogenetic protein (BMP) signaling zebrafish embryo Summary Hemojuvelin (Hjv), a member of the repulsive-guidance molecule (RGM) family, upregulates transcription of the iron regulatory hormone hepcidin by activating the bone morphogenetic protein (BMP) signaling pathway in mammalian cells. Mammalian models have identified furin, neogenin, and matriptase-2 as modifiers of Hjv's function. Using the zebrafish model, we evaluated the effects of hjv and its interacting proteins on hepcidin expression during embryonic development. We found that hjv is strongly expressed in the notochord and somites of the zebrafish embryo and that morpholino knockdown of hjv impaired the development of these structures. Knockdown of hjv or other hjv-related genes, including zebrafish orthologs of furin or neogenin, however, failed to decrease hepcidin expression relative to liver size. In contrast, overexpression of bmp2b or knockdown of matriptase-2 enhanced the intensity and extent of hepcidin expression in zebrafish embryos, but this occurred in an hjv-independent manner. Furthermore, we demonstrated that zebrafish hjv can activate the human hepcidin promoter and enhance BMP responsive gene expression in vitro, but is expressed at low levels in the zebrafish embryonic liver. Taken together, these data support an alternative mechanism for hepcidin regulation during zebrafish embryonic development, which is independent of hjv. Language eng DOI 10.1371/journal.pone.0014553 Field of Research 119999 Medical and Health Sciences not elsewhere classified Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences HERDC Research category C1.1 Refereed article in a scholarly journal Copyright notice ©2011, The Authors Free to Read? Yes Use Rights Persistent URL http://hdl.handle.net/10536/DRO/DU:30062867 Document type: Journal Article Collections: School of Medicine Open Access Collection Related Links Link Description Connect to published version Go to link with your DU access privileges   Connect to Elements publication management system Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Fri, 02 May 2014, 09:13:10 EST Fri, 02 May 2014, 14:25:14 EST Fri, 30 May 2014, 12:48:20 EST Wed, 18 Nov 2015, 06:25:16 EST Mon, 22 May 2017, 12:24:50 EST Filtered Full Citation counts:   Cited 0 times in TR Web of Science Cited 12 times in Scopus Search Google Scholar Access Statistics: 163 Abstract Views, 3 File Downloads  -  Detailed Statistics Created: Fri, 02 May 2014, 09:13:10 EST

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