N-CoR is required for patterning the anterior–posterior axis of zebrafish hindbrain by actively repressing retinoid signaling

Active repression of gene expression mediated by unliganded nuclear receptors plays crucial roles in early development of vertebrates. N-CoR (nuclear receptor co-repressor) is the first identified co-repressor that can repress retinoic acid (RA) inducible gene transcription in the absence of RA. Previously, N-CoR was reported to be required for late-stage organogenesis in mouse but whether N-CoR can affect RA-responsive early embryonic patterning is unknown. In this study, we report molecular cloning of zebrafish orthologue of N-CoR and its wide distribution pattern during zebrafish early development. Knocking down n-cor elevates endogenous RA signaling in zebrafish embryos and posteriorizes the neural ectoderm. Overexpressing or knocking down n-cor in zebrafish embryos alters the length of hindbrain in a manner similar to decreasing or increasing RA signaling in embryos, respectively. Taken together, our results demonstrate that N-CoR is essential for early hindbrain patterning by actively repressing retinoid signaling.