Xbra and Smad-1 cooperate to activate the transcription of neural repressor ventx1.1 in Xenopus embryos

Crosstalk of signaling pathways play crucial roles in cell proliferation, cell differentiation, and cell fate determination for development. In the case of ventx1.1 in Xenopus embryos, both BMP-4/Smad-1 and FGF/Xbra signaling induce the expression of neural repressor ventx1.1. However, the details of how these two pathways interact and lead to neural inhibition by ventx1.1 remain largely unknown. In the present study, Xbra directly bound to the ventx1.1 promoter region and inhibited neurogenesis in a Ventx1.1-dependent manner. Furthermore, Smad-1 and Xbra physically interacted and regulated ventx1.1 transcription in a synergistic fashion. Xbra and Smad-1 interaction cooperatively enhanced the binding of an interacting partner within the ventx1.1 promoter and maximum cooperation was achieved in presence of intact DNA binding sites for both Smad-1 and Xbra. Collectively, BMP-4/Smad-1 and FGF/Xbra signal crosstalk cooperate to activate the transcription of neural repressor ventx1.1 in Xenopus embryos. This suggests that the crosstalk between BMP-4 and FGF signaling negatively regulates early neurogenesis by synergistic activation of ventx1.1 in Xenopus embryos.