Apical constriction is a cell shape change critical to vertebrate neural tube closure, and the contractile force required for this process is generated by actin-myosin networks. The signaling cue that instructs this process has remained elusive. Here, we identify Wnt4 and the transmembrane ephrinB2 protein as playing an instructive role in neural tube closure as members of a signaling complex we termed WERDS (Wnt4, EphrinB2, Ror2, Dishevelled (Dsh2), and Shroom3). Disruption of function or interaction among members of the WERDS complex results in defects of apical constriction and neural tube closure. The mechanism of action involves Wnt4 binding the non-canonical Wnt receptor, Ror2, and enhancing an interaction with ephrinB2, through the main Wnt scaffold protein, Dsh2. This complex in turn recruits the adaptor protein Shroom3, which activates Rho-associated kinase (Rock) to induce apical constriction. Remarkably, we also discovered that a key part of this mechanism is that ephrinB2 antagonizes Wnt/β-catenin signaling through the interaction with Dsh2, which switches Dsh2 function from canonical to non-canonical Wnt signaling that is required for proper neural tube closure.