Dr. Bruce A. Edgar |
|
Fred Hutchinson Cancer Research Center Division of Basic Sciences Member University of Washington College of Arts and Sciences Genetics Affiliate Professor |  |
Mailing AddressFred Hutchinson Cancer Research Center 1100 Fairview Avenue North P.O. Box 19024 B2-152 Seattle, Washington 98109-1024United States | Contact Information |
Qualifications
Ph.D., University of Washington, Genetics, 1987.
Expertise and Research Interests
The development of any animal or plant requires a highly regulated program of cell growth and proliferation. Dr. Edgar's research group studies the genetic logic underlying Drosophila's cell proliferation program, aiming to characterize the different types of cell cycles that occur during development, identify critical regulators of cell growth and proliferation, and understand how these are in turn controlled by developmental programming and environmental factors such as nutrition and infection. We use classical and molecular genetics, cytological assays of cell growth and proliferation, gene expression profiling, and forward genetic screens. We seek to define new genes and mechanisms involved in growth control that will impact general paradigms in cell and developmental biology, and which have relevance to medical conditions involving cell and tissue growth including cancer diagnosis and therapy, stem cell biology and regeneration, wound healing, and metabolic diseases such as diabetes and obesity.
Theme 1: Cell Growth and the Endocycle
Objective: To understand how cell cycle progression is coordinated with cell growth, using endocycling cells.
Overview: Endocycles are simplified cell cycles in which DNA Synthesis and Gap phases alternate without intervening mitoses. Endocycles are used by plants and animals to facilitate post-mitotic cell growth, and are so ubiquitous that they account for about half the earth's biomass. A notable characteristic of Drosophila's endocycles is that their progression is tightly coupled to rates of cell growth. Hence, we are studying these cycles as a model in which to understand the coordination of cell growth with cell cycle progression. We find that endocycles in Drosophila's salivary glands employ a novel biphasic oscillator in which E2F promotes cyclin E (cycE) transcription, CycE/Cdk2 triggers S-phase, and S-phase causes the destruction of E2F via a mechanism similar to that used to destroy the PreRC factor, Cdt1 (Fig 1). Periodic destruction of E2F is essential for endocycle progression, just as periodic destruction of G2-Cyclins is essential for progression of mitotic cell cycles. Furthermore, we find that parameters that alter protein synthesis, such as nutrition or TOR activity, regulate E2F protein levels, and thereby make endocycle progression growth-dependent. Our working hypothesis is that E2F is translationally regulated, and a current objective is to test this idea and determine the underlying mechanism. Many of the regulatory interactions essential to Drosophila's growth-dependent endocycle oscillator are broadly conserved, suggesting that elements of this mechanism may be used in many growth-dependent cell cycles. A long-term objective is to evaluate this view by characterizing plant endocycles, using Arabidopsis genetics.
Theme 2: Developmental Control of Cell Cycle Exit
Objective: To understand the genetic controls that terminate cell proliferation upon terminal differentiation, using the fly wing and eye.
Overview: How are growth and form controlled in development? The regulation of cell proliferation is central to this problem, and the mechanisms controlling cell cycle exit at differentiation are particularly relevant. This project addresses the mechanism of cell cycle exit at differentiation in the Drosophila wing and eye. We have discovered that cell cycle exit involves a "double assurance" mechanism in which the activities of a critical transcription factor, E2F, and a G1 Cyclin/CDK complex, CycE/Cdk2, are independently and dominantly silenced. Bypassing this mechanism by co-expression of E2F and CycE promotes the indefinite proliferation of terminally differentiated cells in vivo. Interestingly, supra-physiological levels of E2F and CyclinE/Cdk2 are required to drive proliferation in differentiating cells. Since the critical targets of both E2F and Cdk2 reside on chromatin at transcriptional promoters and origins of replication, we like the idea that differentiating cells express factors that shield these targets from E2F binding and Cdk2 phosphorylation.
To identify the factors that mediate cell cycle exit, we are performing F1 genetic screens. These employ an E2F-responsive pcna-white+ reporter gene to identify, using eye color, loss- and gain-of-function mutations that allow persistent E2F activity in the differentiating Drosophila eye (Fig 2). Secondary screens then identify those genes that can drive ectopic proliferation. To date we've screened ~180,000 mutant chromosomes covering ~60% of the genome, and ~4000 gain-of-function "EP" transgenics. We've identified 5 mutant loci and >10 overexpressed genes that deregulate E2F activity and drive unscheduled cell proliferation in differentiating wings and eyes. Three loci were expected (E2F, CycE, Ago/Fbw7), but most appear to be novel cell cycle regulators (e.g. Fig 2C-E). We will continue these genetic screens to saturation, and characterize in depth the genes isolated. In addition to the pcna-white+ screens we are using oligonucleotide microarrays to profile the gene expression changes that occur during wing differentiation. These experiments are tracking gene expression during wing differentiation in several genotypes that accomplish cell cycle exit (WT, dp mutants, E2F-overexpressing) and one genotype that bypasses cell cycle exit (co-overexpressed E2F and Cyclin E/Cdk2). The yield of the genetic screens combined with comparative analysis of the microarray data should identify new pathways that mediate cell cycle exit, and provide a paradigm for future studies of how differentiation signals interface with the cell cycle control apparatus to restrain cell proliferation.
Theme 3: Targets of the TSC/Rheb/TOR signaling module
Objective: To identify the molecular pathways via which the TSC1/2 tumor suppressor inhibits cell growth.
Overview: Tuberous sclerosis (TS) is an autosomal dominant disease in which benign tumors arise throughout the body. Most cases are due to loss-of-heterozygosity in TSC1 or TSC2, which encode a protein complex. TSC1/2 restrains cell growth at least in part by inhibiting Rheb, a small GTPase that is an essential activator of the TOR kinase (Fig 3E). TOR regulates metabolic processes required for cell growth including protein synthesis, autophagy, and nutrient storage (Fig 3F, G, H). In vivo, TSC/Rheb/TOR signaling coordinates nutrient availability with cell growth rates. Hence cells mutant for TSC1/2, or overexpressing Rheb, have the striking ability to grow inappropriately without restraint, even in starvation-arrested animals (Fig 3C, D). Although TOR has two well-characterized targets (S6K, 4EBP), genetic analysis in flies and mice indicates that these cannot account for the striking cellular overgrowth phenotypes caused by TSC loss. Moreover, it is unclear that all the effects of TSC mutation are mediated by Rheb and/or TOR. The identification of TOR-independent effectors of the TSC1/2 complex would profoundly alter our understanding of the molecular basis of TS, and strategies for its treatment.
We are taking two approaches to identify new targets of TSC1/2, Rheb, and TOR, and to test whether TSC1/2 executes all its functions via TOR. First, we are using heavy isotope labeling and quantitative mass spectrometry (the SILAC method) to comprehensively characterize the effects of loss-of-TSC function, and gain-of-Rheb function, on the expressed proteome in Drosophila and human cells. Second, we are using fly genetics to screen for suppressors of eye hypertrophy caused by loss of the TSC1/2 complex. Several strong suppressors of TSC1/2 and Rheb have been recovered and are being characterized.
Theme 4: Homeostatic growth in the adult midgut
Objective: To understand how cell-cell interactions, diet, and infection control the proliferation of adult Drosophila midgut stem cells, allowing homeostatic growth.
Overview: Like mammals, adult insects have intestinal stem cells (ISCs) that allow dynamic self-renewal of the gut epithelium. The simplicity of the Drosophila midgut and the fine genetic tools available make this an attractive model for studies of stem cell biology and gut homeostasis, with potential relevance to diseases such as colorectal cancer and inflammatory bowel disease. Drosophila ISCs self-renew, and also generate short-lived differentiated enterocyctes (ECs; absorptive cells that make up the bulk of the intestinal epithelium) and enteroendocrine cells. We find that the induction of pro-apoptotic or stress signals in the ECs results in a burst of stem cell proliferation, allowing the intestine to rapidly regenerate. During regeneration the stem cell pool transiently expands, and then contracts to normal. These observations imply that signaling from spent ECs regulates stem cell proliferation, and that the number of stem cells is regulated according to need. To understand the nature of this regulation we have tested each of the major signaling pathways. We find that dietary stress induces JNK activity in the ECs, and that this triggers their production of a secreted cytokine (Upd3) that signals JAK/STAT activity in the ISCs, stimulating their proliferation. Accordingly, forced JAK/STAT signaling activates ISC proliferation and increases the stem cell pool, yielding grossly hyperplastic midguts. Current studies are investigating the effects of toxic enteric bacteria, and we find that these also stimulate cell turnover and renewal of the midgut epithelium, via JNK and JAK/STAT signaling.
Critical regulatory components that mediate gut homeostasis remain unknown. We are taking two approaches to identify genes that regulate ISC proliferation and differentiation. First, we are performing an F1 genetic screen for genes and RNAi's that cause stem cell hyperplasia when overexpressed. Several novel genes have been identified (e.g. Fig 4). Second, we are using FACS and oligonucleotide microarrays to identify genes expressed specifically in ISCs. Potential ISC regulators identified by these screens will be functionally characterized using all the relevant tools of the Drosophila system. These studies will allow us to develop a working model of how signaling between the different midgut cell types mediates homeostatic growth in the intestine. Novel signaling components and stem cell markers should be discovered, which could be relevant to gut homeostasis and disease in humans. A long term objective, common to all of our developmental studies, is to understand how the signaling pathways that control ISC proliferation interface with the cell cycle control apparatus, and with the systems that regulate cell growth and metabolism.
Theme 1: Cell Growth and the Endocycle
Objective: To understand how cell cycle progression is coordinated with cell growth, using endocycling cells.
Overview: Endocycles are simplified cell cycles in which DNA Synthesis and Gap phases alternate without intervening mitoses. Endocycles are used by plants and animals to facilitate post-mitotic cell growth, and are so ubiquitous that they account for about half the earth's biomass. A notable characteristic of Drosophila's endocycles is that their progression is tightly coupled to rates of cell growth. Hence, we are studying these cycles as a model in which to understand the coordination of cell growth with cell cycle progression. We find that endocycles in Drosophila's salivary glands employ a novel biphasic oscillator in which E2F promotes cyclin E (cycE) transcription, CycE/Cdk2 triggers S-phase, and S-phase causes the destruction of E2F via a mechanism similar to that used to destroy the PreRC factor, Cdt1 (Fig 1). Periodic destruction of E2F is essential for endocycle progression, just as periodic destruction of G2-Cyclins is essential for progression of mitotic cell cycles. Furthermore, we find that parameters that alter protein synthesis, such as nutrition or TOR activity, regulate E2F protein levels, and thereby make endocycle progression growth-dependent. Our working hypothesis is that E2F is translationally regulated, and a current objective is to test this idea and determine the underlying mechanism. Many of the regulatory interactions essential to Drosophila's growth-dependent endocycle oscillator are broadly conserved, suggesting that elements of this mechanism may be used in many growth-dependent cell cycles. A long-term objective is to evaluate this view by characterizing plant endocycles, using Arabidopsis genetics.
Theme 2: Developmental Control of Cell Cycle Exit
Objective: To understand the genetic controls that terminate cell proliferation upon terminal differentiation, using the fly wing and eye.
Overview: How are growth and form controlled in development? The regulation of cell proliferation is central to this problem, and the mechanisms controlling cell cycle exit at differentiation are particularly relevant. This project addresses the mechanism of cell cycle exit at differentiation in the Drosophila wing and eye. We have discovered that cell cycle exit involves a "double assurance" mechanism in which the activities of a critical transcription factor, E2F, and a G1 Cyclin/CDK complex, CycE/Cdk2, are independently and dominantly silenced. Bypassing this mechanism by co-expression of E2F and CycE promotes the indefinite proliferation of terminally differentiated cells in vivo. Interestingly, supra-physiological levels of E2F and CyclinE/Cdk2 are required to drive proliferation in differentiating cells. Since the critical targets of both E2F and Cdk2 reside on chromatin at transcriptional promoters and origins of replication, we like the idea that differentiating cells express factors that shield these targets from E2F binding and Cdk2 phosphorylation.
To identify the factors that mediate cell cycle exit, we are performing F1 genetic screens. These employ an E2F-responsive pcna-white+ reporter gene to identify, using eye color, loss- and gain-of-function mutations that allow persistent E2F activity in the differentiating Drosophila eye (Fig 2). Secondary screens then identify those genes that can drive ectopic proliferation. To date we've screened ~180,000 mutant chromosomes covering ~60% of the genome, and ~4000 gain-of-function "EP" transgenics. We've identified 5 mutant loci and >10 overexpressed genes that deregulate E2F activity and drive unscheduled cell proliferation in differentiating wings and eyes. Three loci were expected (E2F, CycE, Ago/Fbw7), but most appear to be novel cell cycle regulators (e.g. Fig 2C-E). We will continue these genetic screens to saturation, and characterize in depth the genes isolated. In addition to the pcna-white+ screens we are using oligonucleotide microarrays to profile the gene expression changes that occur during wing differentiation. These experiments are tracking gene expression during wing differentiation in several genotypes that accomplish cell cycle exit (WT, dp mutants, E2F-overexpressing) and one genotype that bypasses cell cycle exit (co-overexpressed E2F and Cyclin E/Cdk2). The yield of the genetic screens combined with comparative analysis of the microarray data should identify new pathways that mediate cell cycle exit, and provide a paradigm for future studies of how differentiation signals interface with the cell cycle control apparatus to restrain cell proliferation.
Theme 3: Targets of the TSC/Rheb/TOR signaling module
Objective: To identify the molecular pathways via which the TSC1/2 tumor suppressor inhibits cell growth.
Overview: Tuberous sclerosis (TS) is an autosomal dominant disease in which benign tumors arise throughout the body. Most cases are due to loss-of-heterozygosity in TSC1 or TSC2, which encode a protein complex. TSC1/2 restrains cell growth at least in part by inhibiting Rheb, a small GTPase that is an essential activator of the TOR kinase (Fig 3E). TOR regulates metabolic processes required for cell growth including protein synthesis, autophagy, and nutrient storage (Fig 3F, G, H). In vivo, TSC/Rheb/TOR signaling coordinates nutrient availability with cell growth rates. Hence cells mutant for TSC1/2, or overexpressing Rheb, have the striking ability to grow inappropriately without restraint, even in starvation-arrested animals (Fig 3C, D). Although TOR has two well-characterized targets (S6K, 4EBP), genetic analysis in flies and mice indicates that these cannot account for the striking cellular overgrowth phenotypes caused by TSC loss. Moreover, it is unclear that all the effects of TSC mutation are mediated by Rheb and/or TOR. The identification of TOR-independent effectors of the TSC1/2 complex would profoundly alter our understanding of the molecular basis of TS, and strategies for its treatment.
We are taking two approaches to identify new targets of TSC1/2, Rheb, and TOR, and to test whether TSC1/2 executes all its functions via TOR. First, we are using heavy isotope labeling and quantitative mass spectrometry (the SILAC method) to comprehensively characterize the effects of loss-of-TSC function, and gain-of-Rheb function, on the expressed proteome in Drosophila and human cells. Second, we are using fly genetics to screen for suppressors of eye hypertrophy caused by loss of the TSC1/2 complex. Several strong suppressors of TSC1/2 and Rheb have been recovered and are being characterized.
Theme 4: Homeostatic growth in the adult midgut
Objective: To understand how cell-cell interactions, diet, and infection control the proliferation of adult Drosophila midgut stem cells, allowing homeostatic growth.
Overview: Like mammals, adult insects have intestinal stem cells (ISCs) that allow dynamic self-renewal of the gut epithelium. The simplicity of the Drosophila midgut and the fine genetic tools available make this an attractive model for studies of stem cell biology and gut homeostasis, with potential relevance to diseases such as colorectal cancer and inflammatory bowel disease. Drosophila ISCs self-renew, and also generate short-lived differentiated enterocyctes (ECs; absorptive cells that make up the bulk of the intestinal epithelium) and enteroendocrine cells. We find that the induction of pro-apoptotic or stress signals in the ECs results in a burst of stem cell proliferation, allowing the intestine to rapidly regenerate. During regeneration the stem cell pool transiently expands, and then contracts to normal. These observations imply that signaling from spent ECs regulates stem cell proliferation, and that the number of stem cells is regulated according to need. To understand the nature of this regulation we have tested each of the major signaling pathways. We find that dietary stress induces JNK activity in the ECs, and that this triggers their production of a secreted cytokine (Upd3) that signals JAK/STAT activity in the ISCs, stimulating their proliferation. Accordingly, forced JAK/STAT signaling activates ISC proliferation and increases the stem cell pool, yielding grossly hyperplastic midguts. Current studies are investigating the effects of toxic enteric bacteria, and we find that these also stimulate cell turnover and renewal of the midgut epithelium, via JNK and JAK/STAT signaling.
Critical regulatory components that mediate gut homeostasis remain unknown. We are taking two approaches to identify genes that regulate ISC proliferation and differentiation. First, we are performing an F1 genetic screen for genes and RNAi's that cause stem cell hyperplasia when overexpressed. Several novel genes have been identified (e.g. Fig 4). Second, we are using FACS and oligonucleotide microarrays to identify genes expressed specifically in ISCs. Potential ISC regulators identified by these screens will be functionally characterized using all the relevant tools of the Drosophila system. These studies will allow us to develop a working model of how signaling between the different midgut cell types mediates homeostatic growth in the intestine. Novel signaling components and stem cell markers should be discovered, which could be relevant to gut homeostasis and disease in humans. A long term objective, common to all of our developmental studies, is to understand how the signaling pathways that control ISC proliferation interface with the cell cycle control apparatus, and with the systems that regulate cell growth and metabolism.
Keywords
COS Keywords:
Cell Cycle, Genetics.Languages
(Reading, Writing, Speaking)
German: (Basic, None, Basic)
Honors and Awards
1995-2000,
Rita Allen Scholar,
Rita Allen Foundation
1990-1999,
Lucille P. Markey Scholar,
Lucille P. Markey Charitable Trust
1988-1990,
American Cancer Society Postdoctoral Fellowship,
American Cancer Society
1988, Larry Sandler Memorial Award,
National Drosophila Research Conference
1983-1987,
Predoctoral Fellowship,
National Science Foundation (NSF)
Publications
- Oren-Giladi P, Krieger O, Edgar BA, Chamovitz DA, Segal D (Mar 2008) Cop9 signalosome subunit 8 (CSN8) is essential for Drosophila development., Genes to cells : devoted to molecular & cellular mechanisms, 13 (3), 221-31
- Bandura JL, Edgar BA (Mar 2008) Yorkie and Scalloped: partners in growth activation., Developmental cell, 14 (3), 315-6
- de la Cruz AF, Edgar BA (2008) Flow cytometric analysis of Drosophila cells., Methods in molecular biology (Clifton, N.J.), 420, 373-89
- Grewal SS, Evans JR, Edgar BA (Dec 2007) Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway., The Journal of cell biology, 179 (6), 1105-13
- Buttitta LA, Edgar BA (Dec 2007) Mechanisms controlling cell cycle exit upon terminal differentiation., Current opinion in cell biology, 19 (6), 697-704
- Buttitta LA, Edgar BA (Nov 2007) How size is controlled: from Hippos to Yorkies., Nature cell biology, 9 (11), 1225-7
- O'Keefe DD, Prober DA, Moyle PS, Rickoll WL, Edgar BA (Nov 2007) Egfr/Ras signaling regulates DE-cadherin/Shotgun localization to control vein morphogenesis in the Drosophila wing., Developmental biology, 311 (1), 25-39
- Saucedo, L., Edgar, B. (2007) Filling out the Hippo pathway, Nature Reviews Molecular Cell Biology, 8 (8), 613-621
- Oron, E., Tuller, T., Li, L., Rozovsky, N., Yekutieli, D., Rencus-Lazar, S., Segal, D., Chor, B., Edgar, B.A., Chamovitz, D. (2007) Genomic analysis of COP9 signalosome function in Drosophila melanogaster reveals a role in temporal regulation of gene expression, Molecular Systems Biology, 3, 108
- Buttitta, L.A., Katzaroff, A.J., Perez, C.L., de la Cruz, A., Edgar, B.A. (2007) A Double-Assurance Mechanism Controls Cell Cycle Exit upon Terminal Differentiation in Drosophila, Developmental Cell, 12 (4), 631-643
- Hall, D.J., Grewal, S.S., de la Cruz, A., Edgar, B. (2007) Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila, BMC Biology, 5 (10)
- Edgar, B. (2006) How files get their size: genetics meets physiology, Nature Reviews Genetics, 7 (12), 907
- Datar, S.A., Galloni, M., de la Cruz, A., Marti, M., Edgar, B.A., Frei, C. (2006) Mammalian Cyclin D1/Cdk4 complexes induce cell growth in Drosophila, Cell Cycle, 5, 647-652
- Edgar, B.A. (2006) From Cell structure to transcription: Hippo forges a new path, Cell, 124, 267-273
- Loo LW, Secombe J, Little JT, Carlos LS, Yost C, Cheng PF, Flynn EM, Edgar BA, Eisenman RN (Aug 2005) The transcriptional repressor dMnt is a regulator of growth in Drosophila
melanogaster., Molecular and Cellular Biology, 25 (16), 7078-91
- Grewal SS, Li L, Orian A, Eisenman RN, Edgar BA (Mar 2005) Myc-dependent regulation of ribosomal RNA synthesis during Drosophila
development., Nature Cell Biology, 7 (3), 295-302
- Frei C, Galloni M, Hafen E, Edgar BA (Feb 2005) The Drosophila mitochondrial ribosomal protein mRpL12 is required for
Cyclin D/Cdk4-driven growth., The Embo Journal, 24 (3), 623-34
- Emmerich J, Meyer CA, de la Cruz AF, Edgar BA, Lehner CF (Oct 2004) Cyclin D does not provide essential Cdk4-independent functions in
Drosophila., Genetics, 168 (2), 867-75
- Pierce SB, Yost C, Britton JS, Loo LW, Flynn EM, Edgar BA, Eisenman RN, dMyc is required for larval growth and endoreplication in Drosophila, Development (cambridge, England), 131(10), 2317-27, May 2004
- Reis T, Edgar BA, Negative regulation of dE2F1 by cyclin-dependent kinases controls cell
cycle timing, Cell, 117(2), 253-64, Apr 2004
- Frei C, Edgar BA, Drosophila cyclin D/Cdk4 requires Hif-1 prolyl hydroxylase to drive cell
growth, Developmental Cell, 6(2), 241-51, Feb 2004
- Saucedo LJ, Gao X, Chiarelli DA, Li L, Pan D, Edgar BA, Rheb promotes cell growth as a component of the insulin/TOR signalling
network, Nature Cell Biology, 5(6), 566-71, Jun 2003
- Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D, Rheb is a direct target of the tuberous sclerosis tumour suppressor
proteins, Nature Cell Biology, 5(6), 578-81, Jun 2003
- Orian A, van Steensel B, Delrow J, Bussemaker HJ, Li L, Sawado T, Williams E, Loo LW, Cowley SM, Yost C, Pierce S, Edgar BA, Parkhurst SM, Eisenman RN, Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor
network, Genes & Development, 17(9), 1101-14, May 2003
- Prober DA, Edgar BA, Interactions between Ras1, dMyc, and dPI3K signaling in the developing
Drosophila wing, Genes and Development, 16(17), 2286-99, September 2002
- Britton, J.S., Lockwood, W.B., Cohen, S.M., and Edgar, B.A., Drosophila's Insulin/PI3-Kinase Pathway Coordinates Cellular Metabolism with Nutritional Conditions, Developmental Cell, 2(2), 239-49, February 2002
- Martín-Castellanos, C. and Edgar, B.A., A characterization of the effects of Dpp signaling on cell growth and proliferation in the Drosophila wing, Development, 129(4), 1003-1013, February 2002
- Frank D.J., Edgar B.A., Roth M.B., The Drosophila melanogaster gene brain tumor negatively regulates cell growth and ribosomal RNA synthesis, Development, 129(2), 399-407, January 2002
- Prober, D., Britton, J., de la Cruz, A.F., Johnston, J.A., Lehman, D., Martin-Castellanos, C. (2001) Pattern- and growth-linked cell cycles in Drosophila development In Edgar, B.A. (eds), The Cell Cycle and Development, 1st Edition, John Wiley and Sons, 3-18 pages, ISBN=0471496626 (bookchapter)
- Edgar BA, Orr-Weaver TL, Endoreplication cell cycles: more for less, Cell, 105(3), 297-306, 2001
- Prober DA, Edgar BA, Growth regulation by oncogenes--new insights from model organisms, Current Opinion in Genetics and Development, 11(1), 19-26, February 2001
- Datar, S.A., Jacobs, H.W., de la Cruz, A.F., Lehner, C.F., Edgar, B.A. (2000) The Drosophila Cyclin D-Cdk4 complex promotes cellular growth, EMBO Journal, 19 (17), 4543
- Meyer, C.A., Jacobs, H.W., Datar, S.A., Du, W., Edgar, B.A., Lehner, C.F. (2000) Drosophila Cdk4 is required for normal growth and is dispensable for cell cycle progression, EMBO Journal, 19 (17), 4533-4542
- Prober DA, Edgar BA, Ras1 promotes cellular growth in the Drosophila wing, Cell, 100(4), 435-46, February 2000
- Edgar, BA, From small flies come big discoveries about size control, Nature Cell Biology, 1(8), E191-E193, December 1999
- Johnston LA, Prober DA, Edgar BA, Eisenman RN, Gallant P, Drosophila myc regulates cellular growth during development, Cell, 98(6), 779-90, September 1999
- Migeon JC, Garfinkel MS, Edgar BA, Cloning and characterization of peter pan, a novel Drosophila gene required for larval growth, Molecular Biology of the Cell, 10(6), 1733-44, June 1999
- Galloni M, Edgar BA, Cell-autonomous and non-autonomous growth-defective mutants of Drosophila melanogaster, Development, 126(11), 2365-75, June 1999
- Lehman DA, Patterson B, Johnston LA, Balzer T, Britton JS, Saint R, Edgar BA, Cis-regulatory elements of the mitotic regulator, string/Cdc25, Development, 126(9), 1793-803, May 1999
- Neufeld TP, Edgar BA, Connections between growth and the cell cycle, Current Opinion in Cell Biology, 10(6), 784-90, December 1998
- Johnston LA, Edgar BA, Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing, Nature, 394(6688), 82-4, July 1998
- Neufeld TP, de la Cruz AF, Johnston LA, Edgar BA, Coordination of growth and cell division in the Drosophila wing, Cell, 93(7), 1183-93, June 1998
- Britton JS, Edgar BA, Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms, Development, 125(11), 2149-58, June 1998
- Edgar BA, Lehner CF, Developmental control of cell cycle regulators: a fly's perspective, Science, 274(5293), 1646-52, December 1996
- Edgar BA, Datar SA, Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program, Genes and Development, 10(15), 1966-77, August 1996
- Edgar B, Diversification of cell cycle controls in developing embryos., Curr Opin Cell Biol, 7(6), 815-24, December 1995
- Campbell SD, Sprenger F, Edgar BA, O'Farrell PH (Oct 1995) Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and
phosphorylates Drosophila Cdc2 in vitro., Molecular Biology of the Cell, 6 (10), 1333-47
- Edgar BA, Lehman DA, O'Farrell PH, Transcriptional regulation of string (cdc25): a link between developmental programming and the cell cycle, Development, 120(11), 3131-43, November 1994
- Edgar, B.A. (1994) Cell-cycle control in developmental context, Current Biology, 4 (6), 522-524
- Edwards KA, Montague RA, Shepard S, Edgar BA, Erikson RL, Kiehart DP (May 1994) Identification of Drosophila cytoskeletal proteins by induction of
abnormal cell shape in fission yeast., Proceedings of the National Academy of Sciences of the United States of America., 91 (10), 4589-93
- Edgar BA, Sprenger F, Duronio RJ, Leopold P, O'Farrell PH, Distinct molecular mechanism regulate cell cycle timing at successive stages of Drosophila embryogenesis, Genes and Development, 8(4), 440-52, February 1994
- Schubiger, G., Edgar, B.A. (1994) Using Inhibitors to Study Embryogenesis, Methods in Cell Biology, 44, 697-713
- Foe, V.E., Odell, G.M. (1993) Mitosis and Morphogenesis in the Drosophila Embryo: Point and Counterpoint In Edgar, B.A. (eds), The Development of Drosophila melanogaster, Plainview, NY, Cold Spring Harbor Laboratory Press, 149-300 pages, Submitted, ISBN=0879694238 (bookchapter)
- Edgar BA, O'Farrell PH, The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string, Cell, 62(3), 469-80, August 1990
- O'Farrell PH, Edgar BA, Lakich D, Lehner CF (Nov 1989) Directing cell division during development., Science, 246 (4930), 635-40
- Edgar BA, O'Farrell PH, Genetic control of cell division patterns in the Drosophila embryo, Cell, 57(1), 177-87, April 1989
- Weir MP, Edgar BA, Kornberg T, Schubiger G (Sep 1988) Spatial regulation of engrailed expression in the Drosophila embryo., Genes & Development, 2 (9), 1194-203
- Edgar, B.A., Odell, G.M., Schubiger, G. (1987) Cytoarchitecture and the patterning of fushi tarazu expression in the Drosophila blastoderm., Genes & Development, 1 (10), 1226-1237
- Shinedling S, Singer BS, Gayle M, Pribnow D, Jarvis E, Edgar B, Gold L (Jun 1987) Sequences and studies of bacteriophage T4 rII mutants., Journal of Molecular Biology, 195 (3), 471-80
- Edgar BA, Weir MP, Schubiger G, Kornberg T (Dec 1986) Repression and turnover pattern fushi tarazu RNA in the early Drosophila
embryo., Cell, 47 (5), 747-54
- Edgar BA, Schubiger G (Mar 1986) Parameters controlling transcriptional activation during early Drosophila
development., Cell, 44 (6), 871-7
- Edgar BA, Kiehle CP, Schubiger G (Jan 1986) Cell cycle control by the nucleo-cytoplasmic ratio in early Drosophila development., Cell, 44 (2), 365-72
- Payvar F, DeFranco D, Firestone GL, Edgar B, Wrange O, Okret S, Gustafsson JA, Yamamoto KR (Dec 1983) Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites
within and upstream of the transcribed region., Cell, 35 (2 Pt 1), 381-92
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