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Abstract

Vertebrates have internal asymmetries along the left-right (L-R) axis revealed by organ placement about the midline. In zebrafish, Nodal signaling components are expressed asymmetrically on the left in the lateral plate mesoderm (LPM) and in the diencephalon (DI). The zebrafish gene one-eyed-pinhead (oep) is a member of the EGF–CFC family of proteins that are required cofactors for Nodal signaling. Oep embryos rescued by RNA injection for an early requirement for oep appear wild type but have defects in L-R organ placement in the viscera and the brain. Additionally, asymmetric gene expression in the LPM and DI is never established in these embryos. Similar results were obtained in zebrafish schmalspur mutants that have defects in the Nodal transducer Fast1. In both of these mutants, organs still obtain asymmetric positions, but these positions are randomized with respect to the midline. This indi- cates that Nodal signaling is not required for the generation of asymmetry per se, but is required to direct these asymmetries. Our analysis suggests a model where an early Nodal signaling event leads to a repression of gene expression in the LPM and DI. A later oep-dependent step is required to overcome this repression and allow for gene expression to occur. In addition, we are mapping and cloning several genes that affect L-R development in the zebrafish, and our recent results on this work will be presented.