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

Liver/chemistry
Liver/metabolism
Hemochromatosis/congenital
Animals
Bone Morphogenetic Proteins/metabolism*
Trans-Activators/physiology*
Humans
Promoter Regions, Genetic
Serine Endopeptidases
Signal Transduction*
Hepcidins
Anti-Bacterial Agents
Bone Morphogenetic Protein 2
Embryo, Nonmammalian
Somites/chemistry
Notochord/chemistry
Zebrafish/genetics
Zebrafish/metabolism*
Antimicrobial Cationic Peptides/analysis*
Antimicrobial Cationic Peptides/biosynthesis
Antimicrobial Cationic Peptides/genetics
Zebrafish Proteins/physiology*

(all 22)

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