Notch encodes a transmembrane receptor which mediates the differentiation of the nervous system as well as a very broad spectrum of other regulative decisions during Drosophila development. The developmental action of Notch is general in that it does not appear to mediate specific developmental signals but it rather modulates the ability of precursor cells to respond to such signals. In the past few years it has become clear that the mechanisms of Notch signaling are far more diverse than previously thought. This proposal addresses these new mechanisms.
We aim at the identification of novel downstream effectors which are implied by the genetic analysis and the examination of the documented crosstalk between the Notch and the Ras signaling pathways. Moreover, we propose experiments which will elucidate the functional role of two newly discovered properties of the Notch molecule, its proteolytic cleavage and its apical localization in some, but not all, tissues.
| Hori, Kazuya; Sen, Anindya; Artavanis-Tsakonas, Spyros (2014) Genetic circuitry modulating notch signals through endosomal trafficking. Methods Enzymol 534:283-99 |
| Hori, Kazuya; Sen, Anindya; Artavanis-Tsakonas, Spyros (2013) Notch signaling at a glance. J Cell Sci 126:2135-40 |
| Arboleda-Velasquez, Joseph F; Manent, Jan; Lee, Jeong Hyun et al. (2011) Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease. Proc Natl Acad Sci U S A 108:E128-35 |
| Sun, Youping; Klauzinska, Malgorzata; Lake, Robert J et al. (2011) Trp53 regulates Notch 4 signaling through Mdm2. J Cell Sci 124:1067-76 |
| Fre, Silvia; Hannezo, Edouard; Sale, Sanja et al. (2011) Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice. PLoS One 6:e25785 |
| Hori, Kazuya; Sen, Anindya; Kirchhausen, Tom et al. (2011) Synergy between the ESCRT-III complex and Deltex defines a ligand-independent Notch signal. J Cell Biol 195:1005-15 |
| Kelly, Deborah F; Lake, Robert J; Middelkoop, Teije C et al. (2010) Molecular structure and dimeric organization of the Notch extracellular domain as revealed by electron microscopy. PLoS One 5:e10532 |
| Dimitriadi, Maria; Sleigh, James N; Walker, Amy et al. (2010) Conserved genes act as modifiers of invertebrate SMN loss of function defects. PLoS Genet 6:e1001172 |
| Mourikis, Philippos; Lake, Robert J; Firnhaber, Christopher B et al. (2010) Modifiers of notch transcriptional activity identified by genome-wide RNAi. BMC Dev Biol 10:107 |
| Fre, Silvia; Pallavi, S K; Huyghe, Mathilde et al. (2009) Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine. Proc Natl Acad Sci U S A 106:6309-14 |
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