Genetics, Vol 144, 1127-1141, Copyright © 1996


INVESTIGATIONS

Analysis of Dominant Enhancers and Suppressors of Activated Notch in Drosophila

E. M. Verheyen, K. J. Purcell, M. E. Fortini and S. Artavanis-Tsakonas
Howard Hughes Medical Institute and Departments of Cell Biology and Biology, Yale University, New Haven, Connecticut 06536

The Notch receptor controls cell fate decisions throughout Drosophila development. Truncated, ligand-independent forms of this protein delay or block differentiation. We have previously shown that expression of the intracellular domain of the receptor under the control of the sevenless enhancer/promoter induces a rough eye phenotype in the adult fly. Analysis of the resultant cellular transformations suggested that this form of Notch acts as a constitutively activated receptor. To identify gene products that interact with Notch, a second-site mutagenesis screen was performed to isolate enhancers and suppressors of the eye phenotype caused by expression of these activated Notch molecules. We screened 137,000 mutagenized flies and recovered 290 dominant modifiers. Many new alleles of previously identified genes were isolated, as were mutations defining novel loci that may function in the Notch signaling pathway. We discuss the data with respect to known features of Notch receptor signaling and Drosophila eye development.


This article has been cited by other articles:


Home page
GeneticsHome page
L. R. Braid and E. M. Verheyen
Drosophila Nemo Promotes Eye Specification Directed by the Retinal Determination Gene Network
Genetics, September 1, 2008; 180(1): 283 - 299.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
P. Hayward, T. Kalmar, and A. Martinez Arias
Wnt/Notch signalling and information processing during development
Development, February 1, 2008; 135(3): 411 - 424.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
M. W. Kankel, G. D. Hurlbut, G. Upadhyay, V. Yajnik, B. Yedvobnick, and S. Artavanis-Tsakonas
Investigating the Genetic Circuitry of Mastermind in Drosophila, a Notch Signal Effector
Genetics, December 1, 2007; 177(4): 2493 - 2505.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
A. Simonsen, R. C. Cumming, K. Lindmo, V. Galaviz, S. Cheng, T. E. Rusten, and K. D. Finley
Genetic Modifiers of the Drosophila Blue Cheese Gene Link Defects in Lysosomal Transport With Decreased Life Span and Altered Ubiquitinated-Protein Profiles
Genetics, June 1, 2007; 176(2): 1283 - 1297.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
B. Haarer, S. Viggiano, M. A. Hibbs, O. G. Troyanskaya, and D. C. Amberg
Modeling complex genetic interactions in a simple eukaryotic genome: actin displays a rich spectrum of complex haploinsufficiencies
Genes & Dev., January 15, 2007; 21(2): 148 - 159.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
E. Rottinger, J. Croce, G. Lhomond, L. Besnardeau, C. Gache, and T. Lepage
Nemo-like kinase (NLK) acts downstream of Notch/Delta signalling to downregulate TCF during mesoderm induction in the sea urchin embryo
Development, November 1, 2006; 133(21): 4341 - 4353.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
P. Mourikis, G. D. Hurlbut, and S. Artavanis-Tsakonas
Enigma, a mitochondrial protein affecting lifespan and oxidative stress response in Drosophila
PNAS, January 31, 2006; 103(5): 1307 - 1312.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
J. A. Armstrong, A. S. Sperling, R. Deuring, L. Manning, S. L. Moseley, O. Papoulas, C. I. Piatek, C. Q. Doe, and J. W. Tamkun
Genetic Screens for Enhancers of brahma Reveal Functional Interactions Between the BRM Chromatin-Remodeling Complex and the Delta-Notch Signal Transduction Pathway in Drosophila
Genetics, August 1, 2005; 170(4): 1761 - 1774.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
J. J. Krupp, L. E. Yaich, R. J. Wessells, and R. Bodmer
Identification of Genetic Loci That Interact With cut During Drosophila Wing-Margin Development
Genetics, August 1, 2005; 170(4): 1775 - 1795.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
E. C. Lai, F. Roegiers, X. Qin, Y. N. Jan, and G. M. Rubin
The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta
Development, May 15, 2005; 132(10): 2319 - 2332.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
S. Srinivasan, J. A. Armstrong, R. Deuring, I. K. Dahlsveen, H. McNeill, and J. W. Tamkun
The Drosophila trithorax group protein Kismet facilitates an early step in transcriptional elongation by RNA Polymerase II
Development, April 1, 2005; 132(7): 1623 - 1635.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
K. Weber, N. Johnson, D. Champlin, and A. Patty
Many P-Element Insertions Affect Wing Shape in Drosophila melanogaster
Genetics, March 1, 2005; 169(3): 1461 - 1475.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
H. Kiaris, K. Politi, L. M. Grimm, M. Szabolcs, P. Fisher, A. Efstratiadis, and S. Artavanis-Tsakonas
Modulation of Notch Signaling Elicits Signature Tumors and Inhibits Hras1-Induced Oncogenesis in the Mouse Mammary Epithelium
Am. J. Pathol., August 1, 2004; 165(2): 695 - 705.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
Y. A. Zeng and E. M. Verheyen
Nemo is an inducible antagonist of Wingless signaling during Drosophila wing development
Development, June 15, 2004; 131(12): 2911 - 2920.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
S. Takeo, M. Fujise, T. Akiyama, H. Habuchi, N. Itano, T. Matsuo, T. Aigaki, K. Kimata, and H. Nakato
In Vivo Hyaluronan Synthesis upon Expression of the Mammalian Hyaluronan Synthase Gene in Drosophila
J. Biol. Chem., April 30, 2004; 279(18): 18920 - 18925.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
D. Crowner, K. Madden, S. Goeke, and E. Giniger
Lola regulates midline crossing of CNS axons in Drosophila
Development, March 5, 2003; 129(6): 1317 - 1325.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
B. McCright, J. Lozier, and T. Gridley
A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency
Development, March 4, 2003; 129(4): 1075 - 1082.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
M. T. Pena-Rangel, I. Rodriguez, and J. R. Riesgo-Escovar
A Misexpression Study Examining Dorsal Thorax Formation in Drosophila melanogaster
Genetics, March 1, 2002; 160(3): 1035 - 1050.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
N. Aoyagi and D. A. Wassarman
Developmental and Transcriptional Consequences of Mutations in Drosophila TAFII60
Mol. Cell. Biol., October 15, 2001; 21(20): 6808 - 6819.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
M. Therrien, D. K. Morrison, A. M. Wong, and G. M. Rubin
A Genetic Screen for Modifiers of a Kinase Suppressor of Ras-Dependent Rough Eye Phenotype in Drosophila
Genetics, November 1, 2000; 156(3): 1231 - 1242.
[Abstract] [Full Text]


Home page
GeneticsHome page
S. B. Tanenbaum, S. M. Gorski, J. C. Rusconi, and R. L. Cagan
A Screen for Dominant Modifiers of the irreC-rst Cell Death Phenotype in the Developing Drosophila Retina
Genetics, September 1, 2000; 156(1): 205 - 217.
[Abstract] [Full Text]


Home page
GeneticsHome page
A. Taguchi, K. Sawamoto, and H. Okano
Mutations Modulating the Argos-Regulated Signaling Pathway in Drosophila Eye Development
Genetics, April 1, 2000; 154(4): 1639 - 1648.
[Abstract] [Full Text]


Home page
GeneticsHome page
I. Rebay, F. Chen, F. Hsiao, P. A. Kolodziej, B. H. Kuang, T. Laverty, C. Suh, M. Voas, A. Williams, and G. M. Rubin
A Genetic Screen for Novel Components of the Ras/Mitogen-Activated Protein Kinase Signaling Pathway That Interact With the yan Gene of Drosophila Identifies split ends, a New RNA Recognition Motif-Containing Protein
Genetics, February 1, 2000; 154(2): 695 - 712.
[Abstract] [Full Text]


Home page
GeneticsHome page
N. I. Lukinova, V. V. Roussakova, and M. E. Fortini
Genetic Characterization of Cytological Region 77A-D Harboring the Presenilin Gene of Drosophila melanogaster
Genetics, December 1, 1999; 153(4): 1789 - 1797.
[Abstract] [Full Text]


Home page
GeneticsHome page
A. C. Spradling, D. Stern, A. Beaton, E. J. Rhem, T. Laverty, N. Mozden, S. Misra, and G. M. Rubin
The Berkeley Drosophila Genome Project Gene Disruption Project: Single P-Element Insertions Mutating 25% of Vital Drosophila Genes
Genetics, September 1, 1999; 153(1): 135 - 177.
[Abstract] [Full Text]


Home page
JCBHome page
K. Purcell and S. Artavanis-Tsakonas
The Developmental Role of warthog, the Notch Modifier Encoding Drab6
J. Cell Biol., August 23, 1999; 146(4): 731 - 740.
[Abstract] [Full Text] [PDF]


Home page
ScienceHome page
S. Artavanis-Tsakonas, M. D. Rand, and R. J. Lake
Notch Signaling: Cell Fate Control and Signal Integration in Development
Science, April 30, 1999; 284(5415): 770 - 776.
[Abstract] [Full Text]


Home page
DevelopmentHome page
P zur Lage and A. Jarman
Antagonism of EGFR and notch signalling in the reiterative recruitment of Drosophila adult chordotonal sense organ precursors
Development, January 6, 1999; 126(14): 3149 - 3157.
[Abstract] [PDF]


Home page
DevelopmentHome page
G Daubresse, R Deuring, L Moore, O Papoulas, I Zakrajsek, W. Waldrip, M. Scott, J. Kennison, and J. Tamkun
The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity
Development, January 3, 1999; 126(6): 1175 - 1187.
[Abstract] [PDF]


Home page
GeneticsHome page
M. J. Go and S. Artavanis-Tsakonas
A Genetic Screen for Novel Components of the Notch Signaling Pathway During Drosophila Bristle Development
Genetics, September 1, 1998; 150(1): 211 - 220.
[Abstract] [Full Text]


Home page
DevelopmentHome page
K Matsuno, M. Go, X Sun, D. Eastman, and S Artavanis-Tsakonas
Suppressor of Hairless-independent events in Notch signaling imply novel pathway elements
Development, January 11, 1997; 124(21): 4265 - 4273.
[Abstract] [PDF]


Home page
DevelopmentHome page
D Doherty, L. Jan, and Y. Jan
The Drosophila neurogenic gene big brain, which encodes a membrane-associated protein, acts cell autonomously and can act synergistically with Notch and Delta
Development, January 10, 1997; 124(19): 3881 - 3893.
[Abstract] [PDF]