We examined the roles of Notch signaling in the chondrogenesis of mouse mesencephalic neural crest cells. The present study demonstrated that the activation of Notch signaling or the treatment with fibroblast growth factors (FGFs) promotes the differentiation of proliferative and prehypertrophic chondrocytes expressing collagen type II. Notch activation or FGF2 exposure during the first 24h in ...

BACKGROUND Recent studies have shown that in the developing embryo, arterial and venous identity is established by genetic mechanisms before circulation begins. Vascular endothelial growth factor (VEGF) signaling and its downstream Notch pathway play critical roles in arterial cell fate determination. We have recently shown that Foxc1 and Foxc2, two closely related Fox transcription factors, ar...

Notch signaling regulates multiple developmental processes and is implicated in various human diseases. Through use of the Notch transcriptional co-activator mastermind, we conducted a screen for Notch signal modifiers using the Exelixis collection of insertional mutations, which affects approximately 50% of the Drosophila genome, recovering 160 genes never before associated with Notch, extendi...

OBJECTIVE Notch signaling has a critical role in vascular development and morphogenesis. Activation of Notch in endothelial cells led to a senescence-like phenotype with loss of barrier function. Our objective was to understand the molecular pathways mediating this phenotype. METHODS AND RESULTS Human primary endothelial cells increase expression of Notch receptors and ligands during propagat...

Turning off signaling pathways can be just as important for proper biological regulation as turning them on. The Notch signaling pathway controls development of the nervous system in Drosophila. Proteolysis of Notch appears to initiate signaling, but further proteolysis may also terminate signals from this pathway. Kopan discusses mechanisms that limit signaling by Notch, including recent evide...

Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development ...

Proper organ homeostasis requires tight control of adult stem cells and differentiation through the integration of multiple inputs. In the mouse small intestine, Notch and Wnt signaling are required both for stem cell maintenance and for a proper balance of differentiation between secretory and absorptive cell lineages. In the absence of Notch signaling, stem cells preferentially generate secre...

OBJECTIVE The development of liver fibrosis has been shown to be associated with the transition of quiescent hepatic stellate cells (HSCs) into myofibroblastic HSCs, and the Notch signaling system has been shown to be activated in this process. The Notch signaling pathway is also known to regulate epithelial-mesenchymal transition (EMT). MATERIALS AND METHODS In the current study, quiescent H...

PURPOSE Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and remains refractory to combined-modality therapy in patients with high risk disease. In skeletal myogenesis, Notch signaling prevents muscle differentiation and promotes proliferation of satellite cell progeny. Given its physiologic role in myogenesis and oncogenic role in other human cancers, we hypothesized ...

The Notch signaling pathway controls a large number of processes during animal development and adult homeostasis. One of the conserved post-translational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like (EGF) repeats with a C-X-S-X-(P/A)-C motif by Protein O-glucosyltransferase 1 (POGLUT1; Rumi in Drosophila). Genetic experiments in fli...