Kzp Controls Canonical wnt8 Signaling to Modulate Dorsoventral Patterning during Zebrafish Gastrulation

During vertebrate embryonic development, the body axis formation requires the action of Wnt signals and their antagonists. Zygotic canonical wnt8 expression appears exclusively at the ventrolateral margin and mediates Wnt/β-catenin activities to promote posterior and ventral cell fate. However, the mechanisms involved in the initiation of zygotic wnt8 signals are poorly understood. Here, we identify a novel, maternally derived transcription factor, Kzp (Kaiso zinc finger-containing protein), as an important determinant for the initiation of zygotic Wnt signals in zebrafish. Kzp is a DNA-binding transcription factor that recognizes specific consensus DNA sequences, 5′-(t/a/g)t(a/t/g)nctgcca-3′, through zinc fingers and controls the initiation of zygotic wnt8 expression by directly binding to the wnt8 promoter during zebrafish embryonic development. Depletion of Kzp strongly dorsalized embryos, which was characterized by the expansion of dorsal gene expression. Overexpression of Kzp caused posteriorization. These phenotypes were highly similar to ones induced by wnt8 depletion or overexpression and were rescued by alteration of wnt8 activity. Thus, our results provide the first insight into the mechanism involved in the initiation of zygotic canonical Wnt signals by a maternally derived transcription factor.