The Nrarp gene encodes an ankyrin-repeat protein that is transcriptionallyregulated by the Notch signaling pathway

We have identified a gene encoding a novel protein that is transcriptionall y regulated by the Notch signaling pathway in mammals. This gene, named Nra rp (for Notch-regulated ankyrin-repeat protein), encodes a 114 amino acid p rotein that has a unique amino-terminus and a carboxy-terminal domain conta ining two ankyrin-repeat motifs. A Xenopus homolog of the Nrarp gene was pr eviously identified in a large-scale in situ hybridization screen of random ly isolated cDNA clones. We demonstrate that in T-cell and myoblast cell li nes expression of the Nrarp gene is induced by the intracellular domain of the Notch1 protein, and that this induction is mediated by a CBF1/Su(H)/Lag -1 (CSL)-dependent pathway. During mouse embryogenesis, the Nrarp gene is e xpressed in several tissues in which cellular differentiation is regulated by the Notch signaling pathway. Expression of the Nrarp gene is downregulat ed in Notch1 null mutant mouse embryos, indicating that expression of the N rarp gene is regulated by the Notch pathway in vivo. Thus, Nrarp transcript levels are regulated by the level of Notch1 signaling in both cultured cel l lines and mouse embryos. During somitogenesis, the Nrarp gene is expresse d in a pattern that suggests that Nrarp expression may play a role in the f ormation of somites, and Nrarp expression in the paraxial mesoderm is alter ed in several Notch pathway mutants that exhibit defects in somite formatio n. These observations demonstrate that the Nrarp gene is an evolutionarily conserved transcriptional target of the Notch signaling pathway. (C) 2001 A cademic Press.