Wnt signaling and PKA control Nodal expression and left-right determination in the chick embryo

Expression of the Nodal gene, which encodes a member of the TGF beta superf amily of secreted factors, localizes to the left side of the developing emb ryo in all vertebrates examined so far. This asymmetric pattern correlates with normal development of the left-right axis. We now show that the Wnt an d PKA signaling pathways control left-right determination in the chick embr yo through Nodal. A Wnt/beta -catenin pathway controls Nodal expression in and around Hensen's node, without affecting the upstream regulators Sonic h edgehog, Car and Fibroblast Growth Factor 8. Transcription of Nodal is also positively regulated by a protein kinase A-dependent pathway. Both the adh esion protein N-cadherin and PKI (an endogenous protein kinase A inhibitor) are localized to the right side of the node and may contribute to restrict Nodal activation by Wnt signaling and PKA to the left side of the node.