Several studies have revealed links between hypoxia and activation of Notch in solid tumors. While most reports have focused on intracellular domain of the Notch1 receptor (icN1) stabilization by direct interaction with HIF proteins, little attention has been given to Notch ligand regulation during hypoxia. Here we show that the Notch ligand JAG2 is transcriptionally activated by hypoxia in a H...

The Notch signaling pathway comprises multiple ligands that are used in distinct biological contexts. In principle, different ligands could activate distinct target programs in signal-receiving cells, but it is unclear how such ligand discrimination could occur. Here, we show that cells use dynamics to discriminate signaling by the ligands Dll1 and Dll4 through the Notch1 receptor. Quantitative...

The loss of muscle mass in alcoholic myopathy may reflect alcohol inhibition of myogenic cell differentiation into myotubes. Here, using a high content imaging system we show that ethanol inhibits C2C12 myoblast differentiation by reducing myogenic fusion, creating smaller and less complex myotubes compared with controls. Ethanol administration during C2C12 differentiation reduced MyoD and myog...

The human endometrium undergoes cycle-dependent changes and is only receptive to an implanting blastocyst within a narrow window of 2-4 days in the mid-secretory phase. Such functional require delicate interplay between diversity factors including cytokines signaling pathways. Notch pathway members are expressed endometrium. We have previously demonstrated that ligand Jagged1 (JAG1) localizes e...

Objective—Calcific aortic valve disease is similar to atherosclerosis in that both diseases result from chronic inflammation and endothelial dysfunction. Heterozygous NOTCH1 mutations have been associated to calcific aortic disease and a bicuspid aortic valve. We investigated whether mice with genetic inactivation of the Notch signaling pathway are prone to develop valve disease when exposed to...

PURPOSE The Notch signaling pathway plays crucial roles in regulation of cell proliferation, differentiation and cell fate decision in multiple tissues and cell types. This study was designed to test the effects of enhanced Notch activity on corneal epithelium homeostasis and wound healing using the transgenic mice that overexpressed an activated Notch1 (NICD) in cornea epithelium. METHODS Th...