Direct and indirect control of oral ectoderm regulatory gene expression by Nodal signaling in the sea urchin embryo

► A homeobox gene not is identified as a direct target of Nodal signaling during early sea urchin embryogenesis. ► The not gene is essential in establishing the oral-aboral polarity of the ectodermal regulatory states. ► Nodal signaling through Smad, and indirectly through not, drives progressive expression of oral ectodermal genes.