13 results on '"Bray S"'
Search Results
2. Genome-wide identification of Grainy head targets in Drosophila reveals regulatory interactions with the POU domain transcription factor Vvl.
- Author
-
Yao L, Wang S, Westholm JO, Dai Q, Matsuda R, Hosono C, Bray S, Lai EC, and Samakovlis C
- Subjects
- Animals, Base Sequence, Binding Sites genetics, Drosophila Proteins genetics, Drosophila melanogaster embryology, Embryo, Nonmammalian metabolism, Epithelium metabolism, Gene Expression Regulation, Developmental, Genes, Reporter, Immunity, Innate genetics, Morphogenesis genetics, Organ Specificity genetics, POU Domain Factors metabolism, Protein Binding, Protein Domains, Respiratory System metabolism, Response Elements genetics, DNA-Binding Proteins metabolism, Drosophila Proteins chemistry, Drosophila Proteins metabolism, Drosophila melanogaster genetics, Drosophila melanogaster metabolism, Genome, Insect, POU Domain Factors chemistry, Transcription Factors metabolism
- Abstract
Grainy head (Grh) is a conserved transcription factor (TF) controlling epithelial differentiation and regeneration. To elucidate Grh functions we identified embryonic Grh targets by ChIP-seq and gene expression analysis. We show that Grh controls hundreds of target genes. Repression or activation correlates with the distance of Grh-binding sites to the transcription start sites of its targets. Analysis of 54 Grh-responsive enhancers during development and upon wounding suggests cooperation with distinct TFs in different contexts. In the airways, Grh-repressed genes encode key TFs involved in branching and cell differentiation. Reduction of the POU domain TF Ventral veins lacking (Vvl) largely ameliorates the airway morphogenesis defects of grh mutants. Vvl and Grh proteins additionally interact with each other and regulate a set of common enhancers during epithelial morphogenesis. We conclude that Grh and Vvl participate in a regulatory network controlling epithelial maturation., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)
- Published
- 2017
- Full Text
- View/download PDF
3. Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme.
- Author
-
Terriente-Felix A, Li J, Collins S, Mulligan A, Reekie I, Bernard F, Krejci A, and Bray S
- Subjects
- Animals, Chromatin Immunoprecipitation, Drosophila, Fluorescent Antibody Technique, Hemocytes metabolism, Luciferases, Mutagenesis, Nuclear Proteins metabolism, RNA Interference, Cell Differentiation physiology, Core Binding Factor alpha Subunits metabolism, DNA-Binding Proteins metabolism, Drosophila Proteins metabolism, Hemocytes physiology, Receptors, Notch metabolism, Signal Transduction physiology, Transcription Factors metabolism
- Abstract
The diverse functions of Notch signalling imply that it must elicit context-specific programmes of gene expression. With the aim of investigating how Notch drives cells to differentiate, we have used a genome-wide approach to identify direct Notch targets in Drosophila haemocytes (blood cells), where Notch promotes crystal cell differentiation. Many of the identified Notch-regulated enhancers contain Runx and GATA motifs, and we demonstrate that binding of the Runx protein Lozenge (Lz) is required for enhancers to be competent to respond to Notch. Functional studies of targets, such as klumpfuss (ERG/WT1 family) and pebbled/hindsight (RREB1 homologue), show that Notch acts both to prevent the cells adopting alternate cell fates and to promote morphological characteristics associated with crystal cell differentiation. Inappropriate activity of Klumpfuss perturbs the differentiation programme, resulting in melanotic tumours. Thus, by acting as a master regulator, Lz directs Notch to activate selectively a combination of target genes that correctly locks cells into the differentiation programme.
- Published
- 2013
- Full Text
- View/download PDF
4. Drosophila Hey is a target of Notch in asymmetric divisions during embryonic and larval neurogenesis.
- Author
-
Monastirioti M, Giagtzoglou N, Koumbanakis KA, Zacharioudaki E, Deligiannaki M, Wech I, Almeida M, Preiss A, Bray S, and Delidakis C
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Drosophila Proteins genetics, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Immunohistochemistry, In Situ Hybridization, Larva cytology, Larva growth & development, Larva metabolism, Neurogenesis genetics, Neuroglia metabolism, Neurons cytology, Basic Helix-Loop-Helix Transcription Factors metabolism, Drosophila embryology, Drosophila Proteins metabolism, Neurogenesis physiology, Neurons metabolism, Receptors, Notch metabolism
- Abstract
bHLH-O proteins are a subfamily of the basic-helix-loop-helix transcription factors characterized by an 'Orange' protein-protein interaction domain. Typical members are the Hairy/E(spl), or Hes, proteins, well studied in their ability, among others, to suppress neuronal differentiation in both invertebrates and vertebrates. Hes proteins are often effectors of Notch signalling. In vertebrates, another bHLH-O protein group, the Hey proteins, have also been shown to be Notch targets and to interact with Hes. We have studied the single Drosophila Hey orthologue. We show that it is primarily expressed in a subset of newly born neurons, which receive Notch signalling during their birth. Unlike in vertebrates, however, Hey is not expressed in precursor cells and does not block neuronal differentiation. It rather promotes one of two alternative fates that sibling neurons adopt at birth. Although in the majority of cases Hey is a Notch target, it is also expressed independently of Notch in some lineages, most notably the larval mushroom body. The availability of Hey as a Notch readout has allowed us to study Notch signalling during the genesis of secondary neurons in the larval central nervous system.
- Published
- 2010
- Full Text
- View/download PDF
5. Grainy head controls apical membrane growth and tube elongation in response to Branchless/FGF signalling.
- Author
-
Hemphälä J, Uv A, Cantera R, Bray S, and Samakovlis C
- Subjects
- Animals, Cell Membrane metabolism, Cell Polarity, Cell Size, DNA-Binding Proteins genetics, Drosophila Proteins genetics, Drosophila Proteins metabolism, Drosophila melanogaster physiology, Epithelium growth & development, Genes, Reporter, Immunohistochemistry, Microscopy, Electron, Morphogenesis, Trachea anatomy & histology, Trachea growth & development, Transcription Factors genetics, fas Receptor metabolism, DNA-Binding Proteins metabolism, Fibroblast Growth Factors metabolism, Insect Proteins metabolism, Signal Transduction, Transcription Factors metabolism
- Abstract
Epithelial organogenesis involves concerted movements and growth of distinct subcellular compartments. We show that apical membrane enlargement is critical for lumenal elongation of the Drosophila airways, and is independently controlled by the transcription factor Grainy head. Apical membrane overgrowth in grainy head mutants generates branches that are too long and tortuous without affecting epithelial integrity, whereas Grainy head overexpression limits lumenal growth. The chemoattractant Branchless/FGF induces tube outgrowth, and we find that it upregulates Grainy head activity post-translationally, thereby controlling apical membrane expansion to attain its key role in branching. We favour a two-step model for FGF in branching: first, induction of cell movement and apical membrane growth, and second, activation of Grainy head to limit lumen elongation, ensuring that branches reach and attain their characteristic lengths.
- Published
- 2003
- Full Text
- View/download PDF
6. The Abruptex domain of Notch regulates negative interactions between Notch, its ligands and Fringe.
- Author
-
de Celis JF and Bray SJ
- Subjects
- Animals, Drosophila metabolism, Drosophila Proteins, Female, Gene Expression Regulation, Developmental, Genes, Insect, Genetic Complementation Test, Ligands, Male, Membrane Proteins chemistry, Mutation, Missense, Receptors, Notch, Signal Transduction, Wings, Animal growth & development, Drosophila genetics, Drosophila growth & development, Insect Proteins genetics, Membrane Proteins genetics, Membrane Proteins metabolism, N-Acetylglucosaminyltransferases
- Abstract
The Notch signalling pathway regulates cell fate choices during both vertebrate and invertebrate development. In the Drosophila wing disc, the activation of Notch by its ligands Delta and Serrate is required to make the dorsoventral boundary, where several genes, such as wingless and cut, are expressed in a 2- to 4-cell-wide domain. The interactions between Notch and its ligands are modulated by Fringe via a mechanism that may involve post-transcriptional modifications of Notch. The ligands themselves also help to restrict Notch activity to the dorsoventral boundary cells, because they antagonise the activation of the receptor in the cells where their expression is high. This function of the ligands is critical to establish the polarity of signalling, but very little is known about the mechanisms involved in the interactions between Notch and its ligands that result in suppression of Notch activity. The extracellular domain of Notch contains an array of 36 EGF repeats, two of which, repeats 11 and 12, are necessary for direct interactions between Notch with Delta and Serrate. We investigate here the function of a region of the Notch extracellular domain where several missense mutations, called Abruptex, are localised. These Notch alleles are characterised by phenotypes opposite to the loss of Notch function and also by complex complementation patterns. We find that, in Abruptex mutant discs, only the negative effects of the ligands and Fringe are affected, resulting in the failure to restrict the expression of cut and wingless to the dorsoventral boundary. We suggest that Abruptex alleles identify a domain in the Notch protein that mediates the interactions between Notch, its ligands and Fringe that result in suppression of Notch activity.
- Published
- 2000
- Full Text
- View/download PDF
7. Ectopic expression of individual E(spl) genes has differential effects on different cell fate decisions and underscores the biphasic requirement for notch activity in wing margin establishment in Drosophila.
- Author
-
Ligoxygakis P, Bray SJ, Apidianakis Y, and Delidakis C
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Drosophila, Gene Expression, Homeodomain Proteins, Nerve Tissue Proteins biosynthesis, Nerve Tissue Proteins genetics, Nuclear Proteins biosynthesis, Nuclear Proteins genetics, Proto-Oncogene Proteins genetics, Receptors, Notch, Recombinant Fusion Proteins genetics, Transcription Factors, Wings, Animal, Wnt1 Protein, DNA-Binding Proteins genetics, Drosophila Proteins, Gene Expression Regulation, Developmental, Helix-Loop-Helix Motifs, Insect Proteins genetics, Membrane Proteins metabolism, Repressor Proteins genetics
- Abstract
A common consequence of Notch signalling in Drosophila is the transcriptional activation of seven Enhancer of split [E(spl)] genes, which encode a family of closely related basic-helix-loop-helix transcriptional repressors. Different E(spl) proteins can functionally substitute for each other, hampering loss-of-function genetic analysis and raising the question of whether any specialization exists within the family. We expressed each individual E(spl) gene using the GAL4-UAS system in order to analyse their effect in a number of cell fate decisions taking place in the wing imaginal disk. We focussed on sensory organ precursor determination, wing vein determination and wing pattern formation. All of the E(spl) proteins affect the first two processes in the same way, namely they antagonize neural precursor and vein fates. Yet, the efficacy of this antagonism is quite distinct: E(spl)mbeta has the strongest vein suppression effect, whereas E(spl)m8 and E(spl)m7 are the most active bristle suppressors. During wing patterning, Notch activity orchestrates a complex sequence of events that define the dorsoventral boundary of the wing. We have discerned two phases within this process based on the sensitivity of N loss-of-function phenotypes to concomitant expression of E(spl) genes. E(spl) proteins are initially involved in repression of the vg quadrant enhancer, whereas later they appear to relay the Notch signal that triggers activation of cut expression. Of the seven proteins, E(spl)mgamma is most active in both of these processes. In conclusion, E(spl) proteins have partially redundant functions, yet they have evolved distinct preferences in implementing different cell fate decisions, which closely match their individual normal expression patterns.
- Published
- 1999
- Full Text
- View/download PDF
8. Notch signalling mediates segmentation of the Drosophila leg.
- Author
-
de Celis JF, Tyler DM, de Celis J, and Bray SJ
- Subjects
- Animals, Drosophila melanogaster genetics, Extremities growth & development, Insect Proteins metabolism, Joints, Mutagenesis, Phenotype, Recombination, Genetic, Signal Transduction, Wings, Animal growth & development, X-Rays, Drosophila melanogaster growth & development, Gene Expression Regulation, Developmental, Genes, Insect, Insect Proteins genetics
- Abstract
The legs of Drosophila are divided into segments along the proximodistal axis by flexible structures called joints. The separation between segments is already visible in the imaginal disc as folds of the epithelium, and cells at segment boundaries have different morphology during pupal development. We find that Notch is locally activated in distal cells of each segment, as demonstrated by the restricted expression of the Enhancer of split mbeta gene, and is required for the formation of normal joints. The genes fringe, Delta, Serrate and Suppressor of Hairless, also participate in Notch function during leg development, and their expression is localised within the leg segments with respect to segment boundaries. The failure to form joints when Notch signalling is compromised leads to shortened legs, suggesting that the correct specification of segment boundaries is critical for normal leg growth. The requirement for Notch during leg development resembles that seen during somite formation in vertebrates and at the dorsal ventral boundary of the wing, suggesting that the creation of boundaries of gene expression through Notch activation plays a conserved role in co-ordinating growth and patterning.
- Published
- 1998
- Full Text
- View/download PDF
9. Feed-back mechanisms affecting Notch activation at the dorsoventral boundary in the Drosophila wing.
- Author
-
de Celis JF and Bray S
- Subjects
- Animals, Animals, Genetically Modified, Calcium-Binding Proteins, Clone Cells, Drosophila metabolism, Drosophila Proteins, Feedback, Gene Expression Regulation, Developmental, Genes, Insect, In Situ Hybridization, Insect Proteins metabolism, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Jagged-1 Protein, Ligands, Membrane Proteins metabolism, Models, Biological, Receptors, Notch, Serrate-Jagged Proteins, Signal Transduction, Drosophila genetics, Drosophila growth & development, Insect Proteins genetics, Membrane Proteins genetics, Wings, Animal growth & development, Wings, Animal metabolism
- Abstract
Notch function is required at the dorsoventral boundary of the developing Drosophila wing for its normal growth and patterning. We find that clones of cells expressing either Notch or its ligands Delta and Serrate in the wing mimic Notch activation at the dorsoventral boundary producing non-autonomous effects on proliferation, and activating expression of the target genes E(spl), wingless and cut. The analysis of these clones reveals several mechanisms important for maintaining and delimiting Notch function at the dorsoventral boundary. First, Notch activation in the wing leads to increased production of Delta and Serrate generating a positive feedback loop that maintains signalling. We propose that during normal development, wingless co-operates with Notch to reinforce this positive feedback and Cut, which is activated by Notch at late stages, acts antagonistically to prevent Delta and Serrate expression. Second, high levels of Delta and Serrate have a dominant negative effect on Notch, so that at late stages Notch can only be activated in cells next to the ligand-producing cells. Thus the combined effects of Notch and its target genes cut and wingless regulate the expression of Notch ligands which restrict Notch activity to the dorsoventral boundary.
- Published
- 1997
- Full Text
- View/download PDF
10. Notch signalling regulates veinlet expression and establishes boundaries between veins and interveins in the Drosophila wing.
- Author
-
de Celis JF, Bray S, and Garcia-Bellido A
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors, DNA-Binding Proteins analysis, DNA-Binding Proteins genetics, Genes, Insect physiology, Insect Proteins analysis, Insect Proteins genetics, Intracellular Signaling Peptides and Proteins, Membrane Proteins analysis, Mutation, RNA, Messenger analysis, Receptors, Notch, Repressor Proteins genetics, Veins chemistry, Veins embryology, Veins growth & development, Wings, Animal embryology, Wings, Animal growth & development, Drosophila genetics, Drosophila Proteins, Gene Expression Regulation, Developmental physiology, Membrane Proteins genetics, Signal Transduction physiology, Wings, Animal blood supply
- Abstract
The veins in the Drosophila wing have a characteristic width, which is regulated by the activity of the Notch pathway. The expression of the Notch-ligand Delta is restricted to the developing veins, and coincides with places where Notch transcription is lower. We find that this asymmetrical distribution of ligand and receptor leads to activation of Notch on both sides of each vein within a territory of Delta-expressing cells, and to the establishment of boundary cells that separate the vein from adjacent interveins. In these cells, the expression of the Enhancer of split gene m beta is activated and the transcription of the vein-promoting gene veinlet is repressed, thus restricting vein differentiation. We propose that the establishment of vein thickness utilises a combination of mechanisms that include: (1) independent regulation of Notch and Delta expression in intervein and vein territories, (2) Notch activation by Delta in cells where Notch and Delta expression overlaps, (3) positive feedback on Notch transcription in cells where Notch has been activated and (4) repression of veinlet transcription by E(spl)m beta and maintenance of Delta expression by veinlet/torpedo activity.
- Published
- 1997
- Full Text
- View/download PDF
11. Functional relationships between Notch, Su(H) and the bHLH genes of the E(spl) complex: the E(spl) genes mediate only a subset of Notch activities during imaginal development.
- Author
-
de Celis JF, de Celis J, Ligoxygakis P, Preiss A, Delidakis C, and Bray S
- Subjects
- Animals, Base Sequence, Basic Helix-Loop-Helix Transcription Factors, Drosophila embryology, Drosophila growth & development, Genes, Insect, Helix-Loop-Helix Motifs genetics, Molecular Sequence Data, Mutagenesis, Phenotype, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Notch, Signal Transduction, Transcriptional Activation, Wings, Animal growth & development, DNA-Binding Proteins genetics, Drosophila genetics, Drosophila Proteins, Gene Expression Regulation, Developmental, Insect Hormones genetics, Membrane Proteins genetics, Repressor Proteins genetics, Transcription Factors genetics
- Abstract
The basic helix-loop-helix proteins of the Enhancer of split complex constitute a link between activation of the transmembrane receptor Notch and the resulting effects on transcription of downstream genes. The Suppressor of Hairless protein is the intermediary between Notch activation and expression of all Enhancer of split genes even though individual genes have distinct patterns of expression in imaginal discs. A comparison between the phenotypes produced by Notch, Suppressor of Hairless and Enhancer of split mutations in the wing and thorax indicate that Suppressor of Hairless and Notch requirements are indistinguishable, but that Enhancer of split activity is only essential for a subset of developmental processes involving Notch function. Likewise, the ectopic expression of Enhancer of split proteins does not reproduce all the consequences typical of ectopic Notch activation. We suggest that the Notch pathway bifurcates after the activation of Suppressor of Hairless and that Enhancer of split activity is not required when the consequence of Notch function is the transcriptional activation of downstream genes. Transcriptional activation mediated by Suppressor of Hairless and transcriptional repression mediated by Enhancer of split could provide greater diversity in the response of individual genes to Notch activity.
- Published
- 1996
- Full Text
- View/download PDF
12. Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc.
- Author
-
de Celis JF, Garcia-Bellido A, and Bray SJ
- Subjects
- Alleles, Animals, Calcium-Binding Proteins, Drosophila metabolism, Drosophila Proteins, Female, Gene Expression Regulation, Developmental, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Jagged-1 Protein, Ligands, Male, Membrane Proteins metabolism, Mutation, Phenotype, Receptors, Notch, Serrate-Jagged Proteins, Wings, Animal cytology, Drosophila embryology, Drosophila genetics, Genes, Insect, Membrane Proteins genetics, Wings, Animal embryology, Wings, Animal metabolism
- Abstract
The cells along the dorsoventral boundary of the Drosophila wing imaginal disc have distinctive properties and their specification requires Notch activity. Later in development, these cells will form the wing margin, where sensory organs and specialised trichomes appear in a characteristic pattern. We find that Notch is locally activated in these cells, as demonstrated by the restricted expression of the Enhancer of split proteins in dorsal and ventral cells abutting the D/V boundary throughout the third larval instar. Furthermore other genes identified by their involvement in Notch signaling during neurogenesis, such as Delta and Suppressor of Hairless, also participate in Notch function at the dorsoventral boundary. In addition, Serrate, a similar transmembrane protein to Delta, behaves as a ligand required in dorsal cells to activate Notch at the boundary. Notch gain-of-function alleles in which Notch activity is not restricted to the dorsoventral boundary cause miss-expression of cut and wingless and overgrowth of the disc, illustrating the importance of localised Notch activation for wing development.
- Published
- 1996
- Full Text
- View/download PDF
13. The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo.
- Author
-
Jennings B, Preiss A, Delidakis C, and Bray S
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors, Drosophila genetics, Gene Expression, Genes, Insect, Helix-Loop-Helix Motifs, Immunohistochemistry, Membrane Proteins genetics, Receptors, Notch, DNA-Binding Proteins genetics, Drosophila embryology, Drosophila Proteins, Embryonic Induction, Insect Hormones genetics, Membrane Proteins metabolism, Nervous System embryology, Repressor Proteins, Signal Transduction
- Abstract
The Enhancer of split locus is required during many cell-fate decisions in Drosophila, including the segregation of neural precursors in the embryo. We have generated monoclonal antibodies that recognise some of the basic helix-loop-helix proteins encoded by the Enhancer of split locus and have used them to examine expression of Enhancer of split proteins during neurogenesis. The proteins are expressed in a dynamic pattern in the ventral neurogenic region and are confined to those ectodermal cells that surround a neuroblast in the process of delaminating. There is no staining in the neuroblasts themselves. We have also examined the relationship between Enhancer of split protein accumulation and the Notch signalling pathway. Protein expression is abolished in a number of neurogenic mutant backgrounds, including Notch, but is increased as a result of expressing a constitutively active Notch product. We conclude that Notch signalling activity is directly responsible for the accumulation of basic helix-loop-helix proteins encoded by the Enhancer of split locus.
- Published
- 1994
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.