Regulation of BMP4/Smad1 signaling in the Xenopus gastrula embryo: Roles of TAK1 and miR-26.

The bone morphogenetic protein (BMP) signaling pathway is crucial for ventral mesoderm induction, ectodermal fate determination, and the patterning of the dorsal-ventral axis during Xenopus gastrulation. In this study, new regulatory machineries of the major BMP effector Smad1 are demonstrated on post-translational and translational levels in Xenopus gastrulae. First, on the post-translational level, TGF-beta Activated Kinase 1 (TAK1), another BMP effector, is found to maintain the nuclear translocation of Smad1 by inhibiting the activity of MEK, the upstream activator of Smad1 antagonist erk MAPK. TAK1 also plays a role in the control of the nuclear translocation of Smad1 via forming a complex with it. On the translational level, the miRNA miR-26 is identified to negatively regulate Smad1 via binding to the 3'UTR of Smad1 mRNA, thereby repressing its translation in Xenopus gastrulae. Taken together, my results here may indicate the sophistication of Smad1 regulation at different levels in vertebrate embryonic patterning.