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Development 128, 3189-3195 (2001)
© 2001 The Company of Biologists Limited

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

Concepción Rodríguez-Esteban*, Javier Capdevila*, Yasuhiko Kawakami and Juan Carlos Izpisúa Belmonte{ddagger}

The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
* Equal first authors
{ddagger} Author for correspondence (e-mail belmonte{at}salk.edu )

Accepted 25 May 2001

Expression of the Nodal gene, which encodes a member of the TGFß superfamily of secreted factors, localizes to the left side of the developing embryo in all vertebrates examined so far. This asymmetric pattern correlates with normal development of the left-right axis. We now show that the Wnt and PKA signaling pathways control left-right determination in the chick embryo through Nodal. A Wnt/ß-catenin pathway controls Nodal expression in and around Hensen's node, without affecting the upstream regulators Sonic hedgehog, Car and Fibroblast Growth Factor 8. Transcription of Nodal is also positively regulated by a protein kinase A-dependent pathway. Both the adhesion 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.

Key words: ß-Catenin, Left-right, Nodal, PKA, Sonic hedgehog, TGFß, Wnt, Chick


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© The Company of Biologists Ltd 2001