PUBLICATION
Papp-a2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos
- Authors
- Kjaer-Sorensen, K., Engholm, D.H., Jepsen, M.R., Morch, M.G., Weyer, K., Hefting, L.L., Skov, L.L., Laursen, L.S., Oxvig, C.
- ID
- ZDB-PUB-140923-23
- Date
- 2014
- Source
- Journal of Cell Science 127(23): 5027-37 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Bone Morphogenetic Proteins/genetics
- Bone Morphogenetic Proteins/metabolism
- Cartilage/embryology
- Cartilage/enzymology*
- Gene Expression Regulation, Developmental
- Gene Expression Regulation, Enzymologic
- Gene Knockdown Techniques
- Genotype
- HEK293 Cells
- Humans
- Insulin-Like Growth Factor Binding Protein 3/metabolism
- Insulin-Like Growth Factor Binding Protein 4/metabolism
- Molecular Sequence Data
- Neovascularization, Physiologic*
- Phenotype
- Pregnancy-Associated Plasma Protein-A/genetics
- Pregnancy-Associated Plasma Protein-A/metabolism*
- RNA, Messenger/metabolism
- Receptors, Notch/genetics
- Receptors, Notch/metabolism
- Signal Transduction
- Skull/embryology
- Skull/enzymology*
- Time Factors
- Transfection
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 25236600 Full text @ J. Cell Sci.
Citation
Kjaer-Sorensen, K., Engholm, D.H., Jepsen, M.R., Morch, M.G., Weyer, K., Hefting, L.L., Skov, L.L., Laursen, L.S., Oxvig, C. (2014) Papp-a2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos. Journal of Cell Science. 127(23):5027-37.
Abstract
Pregnancy-associated plasma protein-A2 (PAPP-A2, pappalysin-2) is a large metalloproteinase, known to be required for normal postnatal growth and bone development in mice. We here report the detection of zebrafish papp-a2 mRNA in chordamesoderm, notochord, and lower jaw of zebrafish (Danio rerio) embryos, and that papp-a2 knockdown embryos display broadened axial mesoderm, notochord bends, and severely reduced cranial cartilages. Genetic data link these phenotypes to insulin-like growth factor binding protein-3 (Igfbp-3) and Bmp signaling, and biochemical analysis show specific Igfbp-3 proteolysis by Papp-a2, implicating Papp-a2 in the modulation of Bmp signaling by Igfbp-3 proteolysis. Knockdown of papp-a2 additionally resulted in angiogenesis defects, strikingly similar to previous observations in embryos with mutations in components of the Notch system. Concordantly, we find that Notch signaling is modulated by Papp-a2 in vivo, and, furthermore, that PAPP-A2 is capable of modulating Notch signaling independently of its proteolytic activity in cell culture. Based on these results, we conclude that Papp-a2 modulates Bmp and Notch signaling by independent mechanisms in zebrafish embryos. In conclusion, these data link pappalysin function in zebrafish to two different signaling pathways outside the IGF system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping