BACKGROUND The receptor protein Notch plays a conserved role in restricting neural-fate specification during lateral inhibition. Lateral inhibition requires the Notch intracellular domain to coactivate Su(H)-mediated transcription of the Enhancer-of-split Complex. During Drosophila eye development, Notch plays an additional role in promoting neural fate independently of Su(H) and E(spl)-C, and ...

15 Transcriptional activation of Notch signaling targets requires the formation of a ternary complex 16 that involves the intracellular domain of the Notch receptor (NICD), DNA-binding protein 17 Suppressor of Hairless [Su(H), RPBJ in mammals], and coactivator Mastermind (Mam). Here 18 we report that E(y)1/TAF9, a component of the transcription factor TFIID complex, interacts 19 specifically wi...

Tight regulation of self-renewal and differentiation of adult stem cells ensures that tissues are properly maintained. In the Drosophila intestine, both commitment, i.e. exit from self-renewal, and terminal differentiation are controlled by Notch signaling. Here, we show that distinct requirements for Notch activity exist: commitment requires high Notch activity, whereas terminal differentiatio...

Vascular smooth muscle cell (SMC) fate decisions (cell growth, migration, and apoptosis) are fundamental features in the pathogenesis of vascular disease. We investigated the role of Notch 1 and 3 receptor signaling in controlling adult SMC fate in vitro by establishing that hairy enhancer of split (hes-1 and -5) and related hrt’s (hrt-1, -2, and -3) are direct downstream target genes of Notch ...

The Notch pathway is well known as a master regulator of neural stem cells, but accumulating evidence suggest both novel and sophisticated roles for Notch signaling in adult brain. In the postnatal hippocampus, the regulatory function of Notch signaling on synaptic plasticity has been studied extensively. Mice with germline deletion of Notch1 or presenilins exhibited impaired long-term potentia...

Transforming growth factor beta (TGF-beta) and Notch act as tumor suppressors by inhibiting epithelial cell proliferation. TGF-beta additionally promotes tumor invasiveness and metastasis, whereas Notch supports oncogenic growth. We demonstrate that TGF-beta and ectopic Notch1 receptor cooperatively arrest epithelial growth, whereas endogenous Notch signaling was found to be required for TGF-be...


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 Introduction ....................................................................................................................................1
 The Notch signalling pathway........................................................................................................... 1
 The structure of the Notch genes ....................

Neointima formation causes the failure of 60% of arteriovenous fistulas (AVFs) within 2 years. Neointima-forming mechanisms are controversial but possibly linked to excess proinflammatory responses and dysregulated Notch signaling. To identify how AVFs fail, we anastomosed the carotid artery to the internal jugular vein in normal and uremic mice and compared these findings with those in failed ...

OBJECTIVE To determine the role of Notch signaling in mediating alcohol's inhibition of smooth muscle cell (SMC) proliferation. METHODS AND RESULTS Treatment of human coronary artery SMCs with ethanol (EtOH) decreased Notch 1 mRNA and Notch 1 intracellular domain protein levels, in the absence of any effect on Notch 3. EtOH treatment also decreased C-promoter binding factor-1 (CBF-1)/recombin...

Specification of unequal daughter cell fates in the Drosophila external sense organ lineage requires asymmetric localization of the intrinsic determinant Numb as well as cell-cell interactions mediated by the Delta ligand and Notch receptor. Previous genetic studies indicated that numb acts upstream of Notch, and biochemical studies revealed that Numb can bind Notch. For a functional assay of t...