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 TGFbeta 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/beta-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.
Rodríguez-Esteban
C
C
The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, CA 92037, USA.
Capdevila
J
J
Kawakami
Y
Y
Izpisúa Belmonte
J C
JC
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002642:Chick Embryo; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D008954:Models, Biological; D055457:Nodal Protein; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D015820:Cadherins; D015815:Cell Adhesion Molecules; D053823:Hedgehog Proteins; D055457:Nodal Protein; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D000469:Alkaline Phosphatase