PUBLICATION
Essential role of lysyl oxidases in notochord development
- Authors
- Gansner, J.M., Mendelsohn, B.A., Hultman, K.A., Johnson, S.L., and Gitlin, J.D.
- ID
- ZDB-PUB-070625-5
- Date
- 2007
- Source
- Developmental Biology 307(2): 202-213 (Journal)
- Registered Authors
- Gitlin, Jonathan D., Hultman, Keith, Johnson, Stephen L.
- Keywords
- Zebrafish, Notochord, Lysyl oxidase, Copper, Nutrition, Disease model, col2a1
- MeSH Terms
-
- RNA, Antisense/genetics
- Models, Biological
- Phenotype
- Gene Expression Regulation, Enzymologic
- DNA Primers/genetics
- Collagen Type II/genetics
- Collagen Type II/metabolism
- Animals
- Notochord/abnormalities
- Notochord/embryology*
- Notochord/enzymology*
- Protein-Lysine 6-Oxidase/antagonists & inhibitors
- Protein-Lysine 6-Oxidase/genetics
- Protein-Lysine 6-Oxidase/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Gene Expression Regulation, Developmental
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Base Sequence
- PubMed
- 17543297 Full text @ Dev. Biol.
Citation
Gansner, J.M., Mendelsohn, B.A., Hultman, K.A., Johnson, S.L., and Gitlin, J.D. (2007) Essential role of lysyl oxidases in notochord development. Developmental Biology. 307(2):202-213.
Abstract
Recent studies reveal a critical role for copper in the development of the zebrafish notochord, suggesting that specific cuproenzymes are required for the structural integrity of the notochord sheath. We now demonstrate that beta-aminopropionitrile, a known inhibitor of the copper-dependent lysyl oxidases, causes notochord distortion in the zebrafish embryo identical to that seen in copper deficiency. Characterization of the zebrafish lysyl oxidase genes reveals eight unique sequences, several of which are expressed in the developing notochord. Specific gene knockdown demonstrates that loss of loxl1 results in notochord distortion, and that loxl1 and loxl5b have overlapping roles in notochord formation. Interestingly, while notochord abnormalities are not observed following partial knockdown of loxl1 or loxl5b alone, in each case this markedly sensitizes developing embryos to notochord distortion if copper availability is diminished. Likewise, partial knockdown of the lysyl oxidase substrate col2a1 results in notochord distortion when combined with reduced copper availability or partial knockdown of loxl1 or loxl5b. These data reveal a complex interplay of gene expression and nutrient availability critical to notochord development. They also provide insight into specific genetic and nutritional factors that may play a role in the pathogenesis of structural birth defects of the axial skeleton.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping