Delta-Notch

Notch signaling Delta, Notch, Next, Presenilin, NICD, ADAM, Furin Cancer (T-cell leukemia), Alzheimer s... 

Grandbarbe, L., et al. 2003. Delta-Notch signaling controls the generation of neurons/glia from neural stem cells in a stepwise process. Development 130 1391-1402. 

Lu TM, Luo YJ, Yu JK. BMP and Delta/Notch signaling control the development of amphioxus epidermal sensory neurons insights into the evolution of the peripheral sensory system. Development. 2012 139 2020-30. 

Hammerle, B. Tejedor, F.J. (2007). A novel function of DELTA-NOTCH signalling mediates the transition from proliferation to neurogenesis in neural progenitor cells. PLoS One, Vol. 2(11), ell69. 

Asymmetric cell division is a universal mechanism utilized for the generation of cellular diversity during development (for reviews see Horvitz Herskowitz 1992, Guo Kemphues 1996, Shapiro Losick 1997, Jan Jan 1998). Asymmetric cell divisions during Drosophila embryonic development involve both extrinsic cues mediated through Notch and Delta and intrinsic cell fate determinants and play a major role in producing the distinct cell types which are... 

Itoh, M., et al., Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell, 2003, 4(1), 67-82. 

Fig. 25a provides a comparison of the Charpy notched impact strength (MS) at room temperature of the non-nucleated and of the /(-doped resins (fully -modified with 0.1 wt% calcium pimelate) as a function of the IV of the rubber. Both series show the same trends increasing the IV for the rubbery phase has a positive effect on the toughness. However, the delta between their respective fracture resistance at given IV, A(NIS), is not constant varying between 6% for an IV of 2 dgl-1 to 50% for an IV of 1.7 dg 1 1 ... 

Fig. 25 a Notched impact strength (MS) at room temperature of a non-nucleated and a /(-nucleated PP/EPR model series plotted versus the IV of the rubber phase b particle size, f>w, of the investigated series (from Grein et al. [ 168]) plotted versus the delta in MS, at given IV, between the /(-modified grade and its non-nucleated counterpart... 

Figure 5 Proteolytic processing and signaling of the Notch receptor. In the ER, Notch is cleaved at SI by a furin-like protease to produce a stable heterodimeric receptor that is trafficked to the cell surface. Interaction with ligands such as the proteins Delta and Jagged triggers a shedding of the ectodomain by membrane-tethered metalloprotease-mediated cleavage at S2. The remnant then is cleaved at least twice, at the S3 and S4 sites, to release the Notch counterpart of Ap (Np) and the intracellular domain (NICD). The latter translocates to the nucleus where it interacts with transcription factors to influence gene expression relevant to cell differentiation.

NOTCH proteins participate in conserved pathways that regulate cellular differentiation, proliferation, and cell death. Mammalian NOTCH receptors are single-pass transmembrane proteins that transmit juxtacrine signals initiated by ligands of the Delta, Serrate, or Lag-2 family [122, 123], When ligands bind to the extracellular domain of NOTCH1, sequential proteolytic processing events lead to the... 

Up to now we have discussed reversible signaling pathways, where inactivation is as important as the initial activation. In contrast are essentially irreversible pathways in which a component is proteolytically cleaved. Here we consider two such pathways the NF-kBpathway, which enables cells to respond immediately and vigorously to a number of stress-inducing conditions, and the Notch/Delta pathway, which determines the fates of many types of cells during development. Proteolytic activation of the cell-surface receptor Notch is facilitated by presenllln 1, a membrane protein that also has been Implicated In the pathology of Alzheimer s disease. 

Both Notch and its ligand Delta are transmembrane proteins with numerous EGF-like repeats in their extracellular domains. They participate in a highly conserved and important type of cell differentiation in both Invertebrates and vertebrates, called lateral inhibition, in which adjacent and devel-opmentally equivalent cells assume completely different fates. This process, discussed in detail In Chapter 15, is particularly important in preventing too many nerve precursor cells forming from an undifferentiated layer of epithelial cells. 

---