Notch1 is asymmetrically distributed from the beginning of embryogenesis and controls the ventral center

Based on functional evidence, we have previously demonstrated that early ventral Notch1 activity restricts dorsoanterior development in Xenopus. We found that Notch1 has ventralizing properties and abolishes the dorsalizing activity of beta-catenin by reducing its steady state levels, in a process that does not require beta-catenin phosphorylation by glycogen synthase kinase 3 beta. In the present work, we demonstrate that Notch1 mRNA and protein are enriched in the ventral region from the beginning of embryogenesis in Xenopus. This is the earliest sign of ventral development, preceding the localized expression of wnt8a, bmp4 and Ventx genes in the ventral center and the dorsal accumulation of nuclear beta-catenin. Knockdown experiments indicate that Notch1 is necessary for the normal expression of genes essential for ventral-posterior development. These results indicate that during early embryogenesis ventrally located Notch1 promotes the development of the ventral center. Together with our previous evidence, these results suggest that ventral enrichment of Notch1 underlies the process by which Notch1 participates in restricting nuclear accumulation of beta-catenin to the dorsal side.