Gansner, J.M., Madsen, E.C., Mecham, R.P., and Gitlin, J.D. (2008) Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis. Developmental dynamics : an official publication of the American Association of Anatomists. 237(10):2844-2861.
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.