Osteogenic transcription factor Runx2 is a maternal determinant of dorsoventral patterning in zebrafish.

The maternal genome greatly influences vertebrate embryogenesis before activation of zygotic transcription. Dorsoventral patterning is initiated by maternal factors, but the molecular pathways involved are incompletely understood. In frogs and fish, localized zygotic domains are induced whereby cells either express dorsal or ventral genes. Wnt/beta-catenin signalling promotes expression of the earliest dorsal zygotic genes. Among key zygotic ventralizing factors are the bone morphogenetic proteins (Bmps) and the Vent homeodomain family; the latter act as repressors of dorsal organizer gene transcription. Here we show that Runx2, a transcription factor essential for bone formation, is an important maternal determinant of ventral zygotic genes in zebrafish. Depletion of maternal Runx2b type2 strongly dorsalizes embryos, due to loss of the earliest zygotic expression of vox, vent and ved, resulting in expansion of dorsal gene expression. To date, Runx2b is the only known regulator of vox, vent and ved at the onset of zygotic transcription; we show that this regulation is direct. Runx2 transcripts are processed in mature mouse oocytes and we show that murine Runx2 type2 can substitute for the zebrafish orthologue in its ventralizing function, suggesting that Runx2 may have an evolutionarily conserved role in axis formation.