title: Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis.
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 daddygw1 (pfdgw1). Meiotic mapping and cloning reveal that the pfdgw1 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 pfdgw1 phenotype. Furthermore, each aspect of the pfdgw1 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.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Gansner
authors.forename: Erik C
authors.initials: EC
authors.lastname: Madsen
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mecham
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Gitlin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000196:embryology / Q000378:metabolism; D000071837:Fibrillins; D018507:Gene Expression Regulation, Developmental; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D009024:Morphogenesis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009672:Notochord / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071837:Fibrillins; D008840:Microfilament Proteins; D008249:Protein-Lysine 6-Oxidase