Periodic repression of Notch pathway genes governs the segmentation of Xenopus embryos

During the development of the vertebrate embryo, genes encoding components of the Notch signaling pathway are required for subdividing the paraxial me soderm into repeating segmental structures, called somites. These genes are thought to act in the presomitic mesoderm when cells form prospective somi tes, called somitomeres, but their exact function remains unknown. To addre ss this issue, we have identified two novel genes, called ESR-4 and ESR-5, which are transcriptionally activated in the somitomeres of Xenopus embryos by the Su(H)-dependent Notch signaling pathway. We show that the expressio n of these genes divides each somitomere into an anterior and posterior hal f, and that this pattern of expression is generated by a mechanism that act ively represses the expression of the Notch pathway genes when paraxial cel ls enter a critical region and form a somitomere. Repression of Notch signa ling during somitomere formation requires a negative feedback loop and inhi biting the activity of genes in this loop has a profound effect on somitome re size. Finally we present evidence that once somitomeres form, ESR-5 medi ates a positive feedback loop, which maintains the expression of Notch path way genes. We propose a model in which Notch signaling plays a key role in both establishing and maintaining segmental identity during somitomere form ation in Xenopus embryos.