The Notch signaling pathway is an ancient and highly conserved signaling pathway that controls cell fate specification and tissue patterning in the embryo and in the adult. Region-specific endocardial Notch activity regulates heart morphogenesis through the interaction with multiple myocardial-, epicardial-, and neural crest-derived signals. Mutations in NOTCH signaling elements cause congenita...

Developmental signaling is remarkably robust to environmental variation, including temperature. For example, in ectothermic animals such as Drosophila, Notch signaling is maintained within functional limits across a wide temperature range. We combine experimental and computational approaches to show that temperature compensation of Notch signaling is achieved by an unexpected variety of endocyt...

The canonical Notch signaling pathway mediated by Delta- and Jagged-like Notch ligands determines a variety of cell fates in metazoa. In Caenorhabditis elegans and sea urchins, canonical Notch signaling is essential for different cell fate specifications during early embryogenesis or the formation of endoderm, mesoderm, or ectoderm germ layers. Transcripts of Notch signaling pathway genes are p...

Fringe modulates Notch signaling resulting in the establishment of compartmental boundaries in developing organisms. Fringe is a beta 3N-acetylglucosaminyltransferase (beta 3GlcNAcT) that transfers GlcNAc to O-fucose in epidermal growth factor-like repeats of Notch. Here we use five different Chinese hamster ovary cell glycosylation mutants to identify a key aspect of the mechanism of fringe ac...

In the mammalian liver, bile is transported to the intestine through an intricate network of bile ducts. Notch signaling is required for normal duct formation, but its mode of action has been unclear. Here, we show in mice that bile ducts arise through a novel mechanism of tubulogenesis involving sequential radial differentiation. Notch signaling is activated in a subset of liver progenitor cel...

Recent high-throughput genomic sequencing studies of solid tumors, including head and neck squamous cell carcinoma (SCC), ovarian cancer, lung adenocarcinoma, glioblastoma, breast cancer, and lung SCC, have highlighted DNA mutation as a mechanism for aberrant Notch signaling. A primary challenge of targeting Notch for treatment of solid malignancies is determining whether Notch signaling is can...

Activation of Notch signaling contributes to glioblastoma multiform (GBM) tumorigenesis. However, the molecular mechanism that promotes the Notch signaling augmentation during GBM genesis remains largely unknown. Identification of new factors that regulate Notch signaling is critical for tumor treatment. The expression levels of RND3 and its clinical implication were analyzed in GBM patients. I...

PURPOSE The purpose of this study was to examine the expression and molecular significance of JAG1, a ligand for the Notch developmental signaling pathway, in adrenocortical carcinoma (ACC). EXPERIMENTAL DESIGN Human microarray data were analyzed for genes expressing ligands for the Notch pathway and validated with quantitative real-time PCR (QPCR) and immunoblots of RNA and protein, respecti...

Notch signaling is a major regulator of cell fate, proliferation, and differentiation. Like other signaling pathways, its activity is strongly influenced by intracellular trafficking. Besides contributing to signal activation and down-regulation, differential fluxes between trafficking routes can cause aberrant Notch pathway activation. Investigating the function of the retromer-associated DNAJ...

Notch-Delta signaling is a fundamental cell-cell communication mechanism that governs the differentiation of many cell types. Most existing mathematical models of Notch-Delta signaling are based on a feedback loop between Notch and Delta leading to lateral inhibition of neighboring cells. These models result in a checkerboard spatial pattern whereby adjacent cells express opposing levels of Not...