Fig. 7. A model of 14-3-3 signaling in LR asymmetry in normal and perturbed embryos. Our results suggest the following model. (A) In unmanipulated embryos, endogenous localization machinery ensures that only one cell of a two-cell embryo contains 14-3-3E protein. This protein interacts with an unknown target (see Discussion for probable candidates) whose activation on one side of the midline feeds into the pathway of asymmetric genes. (B) When 14-3-3E protein is misexpressed by the injection of 14-3-3E mRNA immediately after fertilization, excess 14-3-3E protein overwhelms the localization machinery and is present in both cells at the first cleavage. This subsequently provides identical signal to the L and R sides, resulting in a randomization of asymmetry. (C) Exposure to FC in the medium abolishes the asymmetric localization of 14-3-3E (and induces heterotaxia as in B) by competing for its binding with the endogenous localization mechanism. (D) Injection of NR-P peptide abolishes the asymmetry by interfering with the one-sided binding of 14-3-3E to its downstream target.

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