PUBLICATION

BMP Signaling Modulates Hepcidin Expression in Zebrafish Embryos Independent of Hemojuvelin

Authors
Gibert, Y., Lattanzi, V.J., Zhen, A.W., Vedder, L., Brunet, F., Faasse, S.A., Babitt, J.L., Lin, H.Y., Hammerschmidt, M., and Fraenkel, P.G.
ID
ZDB-PUB-110207-19
Date
2011
Source
PLoS One   6(1): e14553 (Journal)
Registered Authors
Brunet, Frederic G., Fraenkel, Paula, Gibert, Yann, Hammerschmidt, Matthias, Vedder, Lea
Keywords
none
MeSH Terms
  • Animals
  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides/analysis*
  • Antimicrobial Cationic Peptides/biosynthesis
  • Antimicrobial Cationic Peptides/genetics
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins/metabolism*
  • Embryo, Nonmammalian
  • Hemochromatosis/congenital
  • Hepcidins
  • Humans
  • Liver/chemistry
  • Liver/metabolism
  • Notochord/chemistry
  • Promoter Regions, Genetic
  • Serine Endopeptidases
  • Signal Transduction*
  • Somites/chemistry
  • Trans-Activators/physiology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/physiology*
PubMed
21283739 Full text @ PLoS One
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes