The Function of Heterodimeric AP-1 Comprised of c-Jun and c-Fos in Activin Mediated Spemann Organizer Gene Expression

BackgroundActivator protein-1 (AP-1) is a mediator of BMP or FGF signaling during Xenopus embryogenesis. However, specific role of AP-1 in activin signaling has not been elucidated during vertebrate development. Methodology/Principal FindingsWe provide new evidence showing that overexpression of heterodimeric AP-1 comprised of c-jun and c-fos (AP-1c-Jun/c-Fos) induces the expression of BMP-antagonizing organizer genes (noggin, chordin and goosecoid) that were normally expressed by high dose of activin. AP-1c-Jun/c-Fos enhanced the promoter activities of organizer genes but reduced that of PV.1, a BMP4-response gene. A loss of function study clearly demonstrated that AP-1c-Jun/c-Fos is required for the activin-induced organizer and neural gene expression. Moreover, physical interaction of AP-1c-Jun/c-Fos and Smad3 cooperatively enhanced the transcriptional activity of goosecoid via direct binding on this promoter. Interestingly, Smad3 mutants at c-Jun binding site failed in regulation of organizer genes, indicating that these physical interactions are specifically necessary for the expression of organizer genes. Conclusions/SignificanceAP-1c-Jun/c-Fos plays a specific role in organizer gene expression in downstream of activin signal during early Xenopus embryogenesis.