PUBLICATION

Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis

Authors
Gansner, J.M., Madsen, E.C., Mecham, R.P., and Gitlin, J.D.
ID
ZDB-PUB-081001-6
Date
2008
Source
Developmental Dynamics : an official publication of the American Association of Anatomists   237(10): 2844-2861 (Journal)
Registered Authors
Gitlin, Jonathan D.
Keywords
zebrafish, fibrillin-2, notochord, copper, lysyl oxidase, caudal vein, congenital contractural arachnodactyly
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Embryo, Nonmammalian/blood supply
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental
  • Microfilament Proteins/deficiency
  • Microfilament Proteins/genetics
  • Microfilament Proteins/metabolism*
  • Microscopy, Electron, Transmission
  • Morphogenesis/genetics*
  • Mutation/genetics
  • Notochord/blood supply
  • Notochord/embryology*
  • Notochord/metabolism*
  • Notochord/ultrastructure
  • Phenotype
  • Protein-Lysine 6-Oxidase/antagonists & inhibitors
  • Protein-Lysine 6-Oxidase/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed
18816837 Full text @ Dev. Dyn.
Abstract
Recent studies demonstrate that lysyl oxidase cuproenzymes are critical for zebrafish notochord formation, but the molecular mechanisms of copper-dependent notochord morphogenesis are incompletely understood. We, therefore, conducted a forward genetic screen for zebrafish mutants that exhibit notochord sensitivity to lysyl oxidase inhibition, yielding a mutant with defects in notochord and vascular morphogenesis, puff daddy(gw1) (pfd(gw1)). Meiotic mapping and cloning reveal that the pfd(gw1) phenotype results from disruption of the gene encoding the extracellular matrix protein fibrillin-2, and the spatiotemporal expression of fibrillin-2 is consistent with the pfd(gw1) phenotype. Furthermore, each aspect of the pfd(gw1) phenotype is recapitulated by morpholino knockdown of fibrillin-2. Taken together, the data reveal a genetic interaction between fibrillin-2 and the lysyl oxidases in notochord formation and demonstrate the importance of fibrillin-2 in specific early developmental processes in zebrafish.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping