Genomes and Genes
Gene Symbol: brk
Alias: BRK, Brk, CG9653, Dm brk, Dmel\CG9653, ssg-1, brinker, CG9653-PA, brk-PA, small salivary glands-1
Species: fruit fly
- Ramirez Weber F, Kornberg T. Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs. Cell. 1999;97:599-607 pubmed..We suggest that cytonemes may be responsible for some forms of long-range cell-cell communication. ..
- Hamaguchi T, Yabe S, Uchiyama H, Murakami R. Drosophila Tbx6-related gene, Dorsocross, mediates high levels of Dpp and Scw signal required for the development of amnioserosa and wing disc primordium. Dev Biol. 2004;265:355-68 pubmed..These results suggest that the Tbx6 subfamily act in the BMP signaling pathway required for embryonic patterning in both animals. ..
- Cook O, Biehs B, Bier E. brinker and optomotor-blind act coordinately to initiate development of the L5 wing vein primordium in Drosophila. Development. 2004;131:2113-24 pubmed..we examine the mechanism by which two broadly expressed Dpp signaling target genes, optomotor-blind (omb) and brinker (brk), collaborate to initiate formation of the fifth longitudinal (L5) wing vein...
- Barrio R, López Varea A, Casado M, de Celis J. Characterization of dSnoN and its relationship to Decapentaplegic signaling in Drosophila. Dev Biol. 2007;306:66-81 pubmed
- Rushlow C, Colosimo P, Lin M, Xu M, Kirov N. Transcriptional regulation of the Drosophila gene zen by competing Smad and Brinker inputs. Genes Dev. 2001;15:340-51 pubmed..of the Dpp signal transducer p-Mad (phosphorylated Mad), together with the recently discovered negative regulator Brinker (Brk), define the spatial limits of zen transcription in a broad dorsal-on/ventral-off domain...
- Kirkpatrick H, Johnson K, Laughon A. Repression of dpp targets by binding of brinker to mad sites. J Biol Chem. 2001;276:18216-22 pubmed..has recently been shown to activate targets such as vestigial (vg) indirectly through negative regulation of brinker (brk). Here we show that the Brk protein functions as a repressor by binding to Dpp response elements...
- Yao L, Phin S, Cho J, Rushlow C, Arora K, Warrior R. Multiple modular promoter elements drive graded brinker expression in response to the Dpp morphogen gradient. Development. 2008;135:2183-92 pubmed publisher..In Drosophila, Decapentaplegic (Dpp), the BMP2/4 homolog, downregulates transcription of the nuclear repressor brinker (brk) in a concentration-dependent manner to generate an inverse graded distribution...
- Gurdon J, Bourillot P. Morphogen gradient interpretation. Nature. 2001;413:797-803 pubmed
- Marty T, Muller B, Basler K, Affolter M. Schnurri mediates Dpp-dependent repression of brinker transcription. Nat Cell Biol. 2000;2:745-9 pubmed..For target genes to be activated, Dpp signalling must suppress transcription of a repressor encoded by the brinker (brk) gene...
- Vuilleumier R, Springhorn A, Patterson L, Koidl S, Hammerschmidt M, Affolter M, et al. Control of Dpp morphogen signalling by a secreted feedback regulator. Nat Cell Biol. 2010;12:611-7 pubmed publisher..We show that Pent interacts with the glypican Dally to control Dpp distribution and provide evidence that proper establishment of the BMP morphogen gradient requires the inbuilt feedback loop embodied by Pent. ..
- Minami M, Kinoshita N, Kamoshida Y, Tanimoto H, Tabata T. brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes. Nature. 1999;398:242-6 pubmed..We report here the molecular cloning of brinker (brk), and show that brk expression is repressed by dpp...
- Jazwinska A, Rushlow C, Roth S. The role of brinker in mediating the graded response to Dpp in early Drosophila embryos. Development. 1999;126:3323-34 pubmedb>Brinker (Brk), a novel protein with features of a transcriptional repressor, regulates the graded response to Decapentaplegic (Dpp) in appendage primordia of Drosophila...
- Von Ohlen T, Doe C. Convergence of dorsal, dpp, and egfr signaling pathways subdivides the drosophila neuroectoderm into three dorsal-ventral columns. Dev Biol. 2000;224:362-72 pubmed
- Hasson P, Muller B, Basler K, Paroush Z. Brinker requires two corepressors for maximal and versatile repression in Dpp signalling. EMBO J. 2001;20:5725-36 pubmed..show that responses to graded Dpp activity also require an input from a complementary and opposing gradient of Brinker (Brk), a transcriptional repressor protein encoded by a Dpp target gene...
- Pyrowolakis G, Hartmann B, Muller B, Basler K, Affolter M. A simple molecular complex mediates widespread BMP-induced repression during Drosophila development. Dev Cell. 2004;7:229-40 pubmed
- Brugger S, Merrill A, Torres Vazquez J, Wu N, Ting M, Cho J, et al. A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos. Development. 2004;131:5153-65 pubmed
- Markstein M, Zinzen R, Markstein P, Yee K, Erives A, Stathopoulos A, et al. A regulatory code for neurogenic gene expression in the Drosophila embryo. Development. 2004;131:2387-94 pubmed..We discuss the prospects for deciphering regulatory codes that link primary DNA sequence information with predicted patterns of gene expression. ..
- Moreno E, Basler K. dMyc transforms cells into super-competitors. Cell. 2004;117:117-29 pubmed..Hence the heritable increase in dMyc levels causes cells to behave as "super-competitors" and reveals a novel mode of clonal expansion that causes, but also relies on, the killing of surrounding cells. ..
- Shravage B, Altmann G, Technau M, Roth S. The role of Dpp and its inhibitors during eggshell patterning in Drosophila. Development. 2007;134:2261-71 pubmed..Drosophila sno (dSno), a homolog of the Ski/Sno family of vertebrate proto-oncogenes, which synergizes with daughters against dpp and brinker to set the posterior and lateral limits of the region, giving rise to dorsal follicle cells.
- Erives A, Levine M. Coordinate enhancers share common organizational features in the Drosophila genome. Proc Natl Acad Sci U S A. 2004;101:3851-6 pubmed..Organized binding sites should facilitate the identification of regulatory codes that link primary DNA sequence information with predicted patterns of gene activity. ..
- Saller E, Bienz M. Direct competition between Brinker and Drosophila Mad in Dpp target gene transcription. EMBO Rep. 2001;2:298-305 pubmedb>Brinker is a nuclear protein that antagonizes Dpp signalling in Drosophila. Its expression is negatively regulated by Dpp...
- Markstein M, Markstein P, Markstein V, Levine M. Genome-wide analysis of clustered Dorsal binding sites identifies putative target genes in the Drosophila embryo. Proc Natl Acad Sci U S A. 2002;99:763-8 pubmed..Three of these regions are associated with known Dorsal target genes: sog, zen, and Brinker. The Dorsal binding cluster in sog is shown to mediate lateral stripes of gene expression in response to low ..
- Zhang H, Levine M, Ashe H. Brinker is a sequence-specific transcriptional repressor in the Drosophila embryo. Genes Dev. 2001;15:261-6 pubmed..Some of these thresholds depend on a putative repressor, Brinker, which is expressed in the neurogenic ectoderm in response to the maternal Dorsal gradient and Dpp signaling...
- Sivasankaran R, Vigano M, Muller B, Affolter M, Basler K. Direct transcriptional control of the Dpp target omb by the DNA binding protein Brinker. EMBO J. 2000;19:6162-72 pubmed..albeit indirect, mode by which Dpp controls the spatial extent of its targets is via the graded downregulation of brinker, whose product in turn negatively regulates the expression of these targets...
- Glinka S, De Lorenzo D, Stephan W. Evidence of gene conversion associated with a selective sweep in Drosophila melanogaster. Mol Biol Evol. 2006;23:1869-78 pubmed..This region, however, was interrupted by gene conversion events leading to a strong haplotype structure in the center of the valley of reduced variation. ..
- Rogulja D, Irvine K. Regulation of cell proliferation by a morphogen gradient. Cell. 2005;123:449-61 pubmed..Conversely, uniform activation of the DPP pathway inhibits cell proliferation in medial wing cells. Our observations provide a direct demonstration that the slope of a morphogen gradient regulates growth during development. ..
- Chopra V, Kong N, Levine M. Transcriptional repression via antilooping in the Drosophila embryo. Proc Natl Acad Sci U S A. 2012;109:9460-4 pubmed publisher..This higher-order mechanism of transcriptional repression has broad implications for the control of gene activity in metazoan development. ..
- Martín F, Pérez Garijo A, Moreno E, Morata G. The brinker gradient controls wing growth in Drosophila. Development. 2004;131:4921-30 pubmed..is recent evidence indicating that the Dpp gradient is converted into an inverse gradient of activity of the gene brinker (brk), which encodes a transcriptional repressor and is negatively regulated by the Dpp pathway...
- Gao S, Steffen J, Laughon A. Dpp-responsive silencers are bound by a trimeric Mad-Medea complex. J Biol Chem. 2005;280:36158-64 pubmed..of the Drosophila Smad proteins, Mad and Medea, binds with high affinity to silencer elements that repress brinker and bag of marbles in response to Dpp signaling...
- Muller B, Hartmann B, Pyrowolakis G, Affolter M, Basler K. Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient. Cell. 2003;113:221-33 pubmed..Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene...
- Portela M, Casas Tinto S, Rhiner C, López Gay J, Dominguez O, Soldini D, et al. Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition. Dev Cell. 2010;19:562-73 pubmed publisher..Overall, we describe the unexpected existence of a physiological mechanism that counteracts cell competition during development. ..
- Adachi Yamada T, O Connor M. Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients. Dev Biol. 2002;251:74-90 pubmed..This phenomenon is likely related to the process of cell competition, and we suggest that it is an evolutionarily important mechanism that helps prevent abnormal tissue specification and growth during development. ..
- Moreno E, Basler K, Morata G. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature. 2002;416:755-9 pubmed..We report here that cell competition requires the function of the brinker (brk) gene, whose expression is normally repressed by Decapentaplegic (Dpp) signalling but is upregulated in slow-..
- Rhiner C, López Gay J, Soldini D, Casas Tinto S, Martín F, Lombardia L, et al. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev Cell. 2010;18:985-98 pubmed publisher..Cell-cell comparison of relative fwe(Lose) and fwe(ubi) levels ultimately determines which cell undergoes apoptosis. This "extracellular code" may constitute an ancient mechanism to terminate competitive conflicts among cells. ..
- Hsiung F, Ramirez Weber F, Iwaki D, Kornberg T. Dependence of Drosophila wing imaginal disc cytonemes on Decapentaplegic. Nature. 2005;437:560-3 pubmed..We also show that the Dpp receptor, Thickveins (Tkv), is present in punctae that move along cytonemes. These observations are consistent with a role for cytonemes in signal transduction. ..
- Bangi E, Wharton K. Dpp and Gbb exhibit different effective ranges in the establishment of the BMP activity gradient critical for Drosophila wing patterning. Dev Biol. 2006;295:178-93 pubmed..The existence of related ligands with different functional ranges may represent a conserved mechanism used in different species to generate robust long range activity gradients. ..
- Qi D, Bergman M, Aihara H, Nibu Y, Mannervik M. Drosophila Ebi mediates Snail-dependent transcriptional repression through HDAC3-induced histone deacetylation. EMBO J. 2008;27:898-909 pubmed publisher..Our results demonstrate that Snail requires the combined activities of Ebi and CtBP, and indicate that histone deacetylation is a repression mechanism in early Drosophila development. ..
- Jazwinska A, Kirov N, Wieschaus E, Roth S, Rushlow C. The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation. Cell. 1999;96:563-73 pubmed..Dpp signals via the SMAD proteins Mad and Medea. Here we show that in the absence of brinker (brk), Mad is not required for the activation of Dpp target genes that depend on low levels of Dpp...
- Schwank G, Restrepo S, Basler K. Growth regulation by Dpp: an essential role for Brinker and a non-essential role for graded signaling levels. Development. 2008;135:4003-13 pubmed publisher..that, as is the case for patterning, Dpp controls wing growth entirely via repression of the target gene brinker (brk)...
- Mizutani C, Meyer N, Roelink H, Bier E. Threshold-dependent BMP-mediated repression: a model for a conserved mechanism that patterns the neuroectoderm. PLoS Biol. 2006;4:e313 pubmed..We propose that BMPs played an ancestral role in patterning the metazoan neuroectoderm by threshold-dependent repression of neural identity genes. ..
- Rebeiz M, Castro B, Liu F, Yue F, Posakony J. Ancestral and conserved cis-regulatory architectures in developmental control genes. Dev Biol. 2012;362:282-94 pubmed publisher..Our examples include a particular Dpp Silencer Element upstream of insect brinker genes, in combination with a novel motif we refer to as the Downstream Element; combinations of a Suppressor of ..
- Campbell G, Tomlinson A. Transducing the Dpp morphogen gradient in the wing of Drosophila: regulation of Dpp targets by brinker. Cell. 1999;96:553-62 pubmed..here we demonstrate that Dpp can also control gene expression indirectly by downregulating the expression of the brinker gene, which encodes a putative transcription factor that functions to repress Dpp targets...
- Baonza A, Freeman M. Notch signalling and the initiation of neural development in the Drosophila eye. Development. 2001;128:3889-98 pubmed..We also report that Notch drives the transition from pre-proneural to proneural by downregulating two repressors of Atonal: Hairy and Extramacrochaetae. ..
- Gibson M, Perrimon N. Extrusion and death of DPP/BMP-compromised epithelial cells in the developing Drosophila wing. Science. 2005;307:1785-9 pubmed..We propose that in addition to assigning cell fates, a crucial developmental function of DPP/BMP signaling is the position-specific control of epithelial architecture. ..
- Walsh C, Carroll S. Collaboration between Smads and a Hox protein in target gene repression. Development. 2007;134:3585-92 pubmed publisher..These results support an emerging view of Hox proteins acting in collaboration with a much more diverse set of transcription factors than has generally been appreciated...
- Moser M, Campbell G. Generating and interpreting the Brinker gradient in the Drosophila wing. Dev Biol. 2005;286:647-58 pubmedThe transcription factor Brinker (Brk) represses gene expression in the Drosophila wing imaginal disc, where it is expressed in symmetrical lateral-to-medial gradients, a pattern that is established by inverse gradients of the TGF-beta, ..
- Cande J, Goltsev Y, Levine M. Conservation of enhancer location in divergent insects. Proc Natl Acad Sci U S A. 2009;106:14414-9 pubmed publisher..The most dramatic example of this conservation is seen for the "shadow" enhancer regulating brinker: It is conserved within the intron of the neighboring Atg5 locus of both flies and mosquitoes...
- Ratnaparkhi G, Jia S, Courey A. Uncoupling dorsal-mediated activation from dorsal-mediated repression in the Drosophila embryo. Development. 2006;133:4409-14 pubmed..This indicates that dorsoventral patterning is not dependent upon Dorsal-mediated repression, reflecting the existence of redundant mechanisms to block Decapentaplegic signaling. ..
- Song H, Hasson P, Paroush Z, Courey A. Groucho oligomerization is required for repression in vivo. Mol Cell Biol. 2004;24:4341-50 pubmed..Although the function of several corepressors is suspected to involve oligomerization, these studies represent one of the first direct links between corepressor oligomerization and repression in vivo. ..
- Cornell R, Ohlen T. Vnd/nkx, ind/gsh, and msh/msx: conserved regulators of dorsoventral neural patterning?. Curr Opin Neurobiol. 2000;10:63-71 pubmed..The three-column expression pattern may thus represent a developmental mechanism that is more resistant to evolutionary changes than genetic events upstream or downstream of it. ..
- Weiss A, Charbonnier E, Ellertsdottir E, Tsirigos A, Wolf C, Schuh R, et al. A conserved activation element in BMP signaling during Drosophila development. Nat Struct Mol Biol. 2010;17:69-76 pubmed publisher..a consequence, the AE does not recruit Schnurri but rather integrates repressive input by the default repressor Brinker and activating input by the Smad signal transducers Mothers against Dpp (Mad) and Medea via competitive DNA ..
- Yao L, Blitz I, Peiffer D, Phin S, Wang Y, Ogata S, et al. Schnurri transcription factors from Drosophila and vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism. Development. 2006;133:4025-34 pubmed..homolog Decapentaplegic (Dpp), by forming a Shn/Smad repression complex on defined promoter elements in the brinker (brk) gene. Brk is a transcriptional repressor that downregulates Dpp target genes...
- Yagi R, Mayer F, Basler K. Refined LexA transactivators and their use in combination with the Drosophila Gal4 system. Proc Natl Acad Sci U S A. 2010;107:16166-71 pubmed publisher..The optimized LexA system facilitates precise analyses of complex biological phenomena and signaling pathways in Drosophila. ..
- Teleman A, Cohen S. Dpp gradient formation in the Drosophila wing imaginal disc. Cell. 2000;103:971-80 pubmed..The pMAD gradient adjusted to compartment size when this was experimentally altered. These observations suggest that the Dpp activity gradient may be shaped at the level of receptor activation. ..
- Torres Vazquez J, Park S, Warrior R, Arora K. The transcription factor Schnurri plays a dual role in mediating Dpp signaling during embryogenesis. Development. 2001;128:1657-70 pubmed..two distinct mechanisms: direct activation of target genes and relief of repression by the nuclear protein Brinker (Brk)...
- Foronda D, Pérez Garijo A, Martín F. Dpp of posterior origin patterns the proximal region of the wing. Mech Dev. 2009;126:99-106 pubmed publisher..Since there is a similar expression in the haltere disc, we suggest that this late appearing posterior Dpp activity may be an attribute of dorsal thoracic discs. ..
- Crocker J, Tamori Y, Erives A. Evolution acts on enhancer organization to fine-tune gradient threshold readouts. PLoS Biol. 2008;6:e263 pubmed publisher..Our study demonstrates that equivalence classes of CRMs are powerful tools for detecting lineage-specific adaptations by gene regulatory sequences. ..
- Rusten T, Cantera R, Kafatos F, Barrio R. The role of TGF beta signaling in the formation of the dorsal nervous system is conserved between Drosophila and chordates. Development. 2002;129:3575-84 pubmed..Double mutant analysis of the Decapentaplegic signaling mediator Schnurri and the inhibitor Brinker indicates that formation of these neurons requires Decapentaplegic signaling, and their absence in the mutant is ..
- Abrams J. Competition and compensation: coupled to death in development and cancer. Cell. 2002;110:403-6 pubmed..Recent insights from the Drosophila system implicate new determinants that specify "winners" and "losers" in this process. ..
- Cremazy F, Berta P, Girard F. Sox neuro, a new Drosophila Sox gene expressed in the developing central nervous system. Mech Dev. 2000;93:215-9 pubmed..We present strong evidence that the early SoxN neuroectoderm expression is controlled by the zygotic dorso-ventral patterning genes (dpp, sog, brk, twi).
- Klinedinst S, Bodmer R. Gata factor Pannier is required to establish competence for heart progenitor formation. Development. 2003;130:3027-38 pubmed..In support, we find that manipulation of pannier activity in either germ layer affects cardiac specification, suggesting that its function is required in both the mesoderm and the ectoderm. ..
- Lilja T, Qi D, Stabell M, Mannervik M. The CBP coactivator functions both upstream and downstream of Dpp/Screw signaling in the early Drosophila embryo. Dev Biol. 2003;262:294-302 pubmed..These results highlight the exceptional sensitivity of components in the TGF-beta signaling pathway to a decline in CBP concentration. ..
- Takaesu N, Bulanin D, Johnson A, Orenic T, Newfeld S. A combinatorial enhancer recognized by Mad, TCF and Brinker first activates then represses dpp expression in the posterior spiracles of Drosophila. Dev Biol. 2008;313:829-43 pubmed..There is also a binding site for Brinker likely employed to repress dppMX expression...