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

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.