The generation of left-right (LR) patterning depends on the activity of Cerberus-related proteins in the node region. Charon (zebrafish) and Cerberus-like-2 (Cerl-2; mouse) prevent the spread of the Nodal signal to the right side in developing embryos, but the role of the chick Cerberus-related protein (cCer) in LR patterning has been less clear. However, its role is now clarified by Belo and co-workers, who report that Nodal activates cCer transcription in the left-side mesoderm; cCer then negatively regulates Nodal signalling (). From the cCer promoter, they identify a left-side enhancer that contains FOXH1- and SMAD-binding sites and that is Nodal responsive. This element is sufficient to induce cCer transcription in the left side, and cCer overexpression in the left side represses Nodal expression. Significantly, ectopic Nodal expression occurs in the right side of cCer-knockdown embryos. These results reveal cCer as a negative regulator of Nodal asymmetric signalling and indicate that cCer appears to have a similar role to Charon and Cerl-2 in restricting Nodal activity to the left side.
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