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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS026084-06A1
Application #
2265798
Study Section
Neurology C Study Section (NEUC)
Project Start
1988-04-01
Project End
1999-01-31
Budget Start
1995-04-04
Budget End
1996-01-31
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Yale University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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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