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
  • Notochord/abnormalities
  • Notochord/embryology*
  • Notochord/enzymology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Gene Expression Regulation, Enzymologic
  • Protein-Lysine 6-Oxidase/antagonists & inhibitors
  • Protein-Lysine 6-Oxidase/genetics
  • Protein-Lysine 6-Oxidase/metabolism*
  • Gene Expression Regulation, Developmental
  • Animals
  • RNA, Antisense/genetics
  • DNA Primers/genetics
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Collagen Type II/genetics
  • Collagen Type II/metabolism
  • Models, Biological
  • Base Sequence
  • Phenotype
(all 22)
PubMed
17543297 Full text @ Dev. Biol.
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
Figures
Figure Gallery (10 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
col2a1aMO1-col2a1aMRPHLNO
loxl1MO1-loxl1MRPHLNO
loxl1MO2-loxl1MRPHLNO
loxl1MO3-loxl1MRPHLNO
loxl2bMO1-loxl2bMRPHLNO
loxl3bMO1-loxl3bMRPHLNO
loxl5bMO1-loxl5bMRPHLNO
loxl5bMO2-loxl5bMRPHLNO
1 - 8 of 8
Show
Fish
Antibodies
No data available
Orthology
1 - 6 of 6
Show
Engineered Foreign Genes
No data available
Mapping
No data available