PUBLICATION
Crossveinless 2 is an essential positive feedback regulator of Bmp signaling during zebrafish gastrulation
- Authors
- Rentzsch, F., Zhang, J., Kramer, C., Sebald, W., and Hammerschmidt, M.
- ID
- ZDB-PUB-060130-9
- Date
- 2006
- Source
- Development (Cambridge, England) 133(5): 801-811 (Journal)
- Registered Authors
- Hammerschmidt, Matthias, Rentzsch, Fabian
- Keywords
- Zebrafish, Crossveinless 2, Bmp
- MeSH Terms
-
- Animals
- Body Patterning/genetics*
- Bone Morphogenetic Proteins/genetics
- Bone Morphogenetic Proteins/metabolism*
- Embryo, Nonmammalian/metabolism
- Epistasis, Genetic
- GTPase-Activating Proteins/genetics
- GTPase-Activating Proteins/metabolism*
- Gastrula/cytology
- Gastrula/metabolism
- Glycoproteins/genetics
- Glycoproteins/metabolism
- Intercellular Signaling Peptides and Proteins/genetics
- Intercellular Signaling Peptides and Proteins/metabolism
- Mutation
- Signal Transduction
- Up-Regulation/genetics*
- Zebrafish/embryology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 16439480 Full text @ Development
Citation
Rentzsch, F., Zhang, J., Kramer, C., Sebald, W., and Hammerschmidt, M. (2006) Crossveinless 2 is an essential positive feedback regulator of Bmp signaling during zebrafish gastrulation. Development (Cambridge, England). 133(5):801-811.
Abstract
Signaling by bone morphogenetic proteins (Bmps) plays a pivotal role in developmental and pathological processes, and is regulated by a complex interplay with secreted Bmp binding factors, including Crossveinless 2 (Cvl2). Although structurally related to the Bmp antagonist Chordin, Crossveinless 2 has been described to be both a Bmp agonist and antagonist. Here, we present the first loss-of-function study of a vertebrate cvl2 homologue, showing that zebrafish cvl2 is required in a positive feedback loop to promote Bmp signaling during embryonic dorsoventral patterning. In vivo, Cvl2 protein undergoes proteolytic cleavage and this cleavage converts Cvl2 from an anti- to a pro-Bmp factor. Embryonic epistasis analyses and protein interaction assays indicate that the pro-Bmp function of Cvl2 is partly accomplished by competing with Chordin for binding to Bmps. Studies in cell culture and embryos further suggest that the anti-Bmp effect of uncleaved Cvl2 is due to its association with the extracellular matrix, which is not found for cleaved Cvl2. Our data identify Cvl2 as an essential pro-Bmp factor during zebrafish embryogenesis, emphasizing the functional diversity of Bmp binding CR-domain proteins. Differential proteolytic processing as a mode of regulation might account for anti-Bmp effects in other contexts.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping