Retinoic acid signaling regulates development of the dorsal forebrain midline and the choroid plexus in the chick

The developing forebrain roof plate (RP) contains a transient signaling center, perturbations in which have been linked to holoprosencephaly (HPE). Here, we describe a novel domain of retinoic acid (RA) signaling that is specific to the chick RP and demonstrate that RA signaling is sufficient for inducing characteristics of the RP in ectopic locations. We further demonstrate that, unlike what has been observed in the mouse, RA signaling is essential for invagination of the RP in chick, failure of which leads to an HPE-like phenotype. In addition, we found that RA exerts a negative influence on choroid plexus differentiation. Thus, our findings identify RA as a novel regulator of chick forebrain RP development.