PUBLICATION
Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis
- Authors
- Anderson, C., Bartlett, S.J., Gansner, J.M., Wilson, D., He, L., Gitlin, J.D., Kelsh, R.N., and Dowden, J.
- ID
- ZDB-PUB-070122-32
- Date
- 2007
- Source
- Molecular Biosystems 3(1): 51-59 (Journal)
- Registered Authors
- Bartlett, Stephen, Gitlin, Jonathan D., Kelsh, Robert
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/enzymology
- Metals/metabolism
- Molecular Structure
- Morphogenesis/genetics*
- Notochord/abnormalities
- Notochord/drug effects
- Notochord/embryology*
- Notochord/enzymology
- Protein-Lysine 6-Oxidase/metabolism
- Protein-Lysine 6-Oxidase/physiology*
- Pyridines/pharmacology
- Sulfhydryl Compounds/pharmacology
- Thiones/pharmacology
- Time Factors
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 17216056 Full text @ Mol. Biosyst.
Citation
Anderson, C., Bartlett, S.J., Gansner, J.M., Wilson, D., He, L., Gitlin, J.D., Kelsh, R.N., and Dowden, J. (2007) Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis. Molecular Biosystems. 3(1):51-59.
Abstract
As a result of a chemical genetic screen for modulators of metalloprotease activity, we report that 2-mercaptopyridine-N-oxide induces a conspicuous undulating notochord defect in zebrafish embryos, a phenocopy of the leviathan mutant. The location of the chemically-induced wavy notochord correlated with the timing of application, thus defining a narrow chemical sensitivity window during segmentation stages. Microscopic observations revealed that notochord undulations appeared during the phase of notochord cell vacuolation and notochord elongation. Notochord cells become swollen as well as disorganized, while electron microscopy revealed disrupted organization of collagen fibrils in the surrounding sheath. We demonstrate by assay in zebrafish extracts that 2-mercaptopyridine-N-oxide inhibits lysyl oxidase. Thus, we provide insight into notochord morphogenesis and reveal novel compounds for lysyl oxidase inhibition. Taken together, these data underline the utility of small molecules for elucidating the dynamic mechanisms of early morphogenesis and provide a potential explanation for the recently established role of copper in zebrafish notochord formation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping