Notch codes for a transmembrane receptor which mediates the differentiation of the nervous system as well as a variety of other tissues involving regulative decisions during Drosophila development. The overall aim of this proposal is to contribute to the dissection of the Notch pathway. Within this framework, we are specifically interested in addressing the function of the intracellular domain of the Notch molecule in an attempt to gain insight into the nature of the signal that the Notch receptor mediates. Several genetic screens are proposed in order to identify interaction partners of Notch and the molecular characterization of these partners is anticipated. In addition a documented molecular interaction between the intracellular domain of Notch and one of its genetic interaction partners deltex and suppressor of Hairless, will be further characterized. Finally, genes which are capable of interacting with deltex will also be identified and characterized.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurology C Study Section (NEUC)
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Yale University
Anatomy/Cell Biology
Schools of Medicine
New Haven
United States
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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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