Maternal Eomesodermin regulates zygotic nodal gene expression for mesendoderm induction in zebrafish embryos

Development of animal embryos before zygotic genome activation at the midblastula transition (MBT) is essentially supported by egg-derived maternal products. Nodal proteins are crucial signals for mesoderm and endoderm induction after the MBT. It remains unclear which maternal factors activate zygotic expression of nodal genes in the ventrolateral blastodermal margin of the zebrafish blastulas. In this study, we show that loss of maternal Eomesodermin a (Eomesa), a T-box transcription factor, impairs zygotic expression of the nodal genes ndr1 and ndr2 as well as mesodermal and endodermal markers, indicating an involvement in mesendoderm induction. Maternal Eomesa is also required for timely zygotic expression of the transcription factor gene mxtx2, a regulator of nodal gene expression. Eomesa directly binds to the Eomes-binding sites in the promoter or enhancer of ndr1, ndr2, and mxtx2 to activate their transcription. Furthermore, human and mouse Nodal genes are also regulated by Eomes. Transfection of zebrafish eomesa into murine embryonic stem cells promotes mesendodermal differentiation with constant higher levels of endogenous Nodal expression, suggesting a conserved function of Eomes. Taken together, our findings reveal a conserved role of maternal T-box transcription factors in regulating nodal gene expression and mesendoderm induction in vertebrate embryos.