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S Bray

Publications and source records attributed to S Bray.

32 records · Page 2Linked to original sources
PubMed1998

Notch signalling in Drosophila: three ways to use a pathway.

Cell-cell interactions mediated by Notch are critical at multiple stages of development. Our current understanding of the Notch signalling pathway suggests a comparatively simple transduction mechanism. However, this core pathway can be deployed in three different types of developmental process: lateral inhibition, lineage decisions and boundary formation. These illustrate how the activity of the pathway can be modulated both at the cell surface, through availability and effectiveness of ligand interactions, and inside the cell, through effects on the transduction pathway and the responsiveness of target genes.

Animals↗
PubMed1998

Homeotic regulation of segment-specific differences in neuroblast numbers and proliferation in the Drosophila central nervous system.

The number and pattern of neuroblasts that initially segregate from the neuroectoderm in the early Drosophila embryo is identical in thoracic and abdominal segments. However, during late embryogenesis differences in the numbers of neuroblasts and in the extent of neuroblast proliferation arise between these regions. We show that the homeotic genes Ultrabithorax and abdominal-A regulate these late differences, and that misexpression of either gene in thoracic neuroblasts after segregation is sufficient to induce abdominal behaviour. However, in wild type embryos we only detect abdominal-A and Ultrabithorax proteins in early neuroblasts. Furthermore, transplantation experiments reveal that segment-specific behaviour is determined prior to neuroblast segregation. Thus, the segment-specific differences in neuroblast behaviour seem to be determined in the early embryo, mediated through the expression of homeotic genes in early neuroblasts, and executed in later programmes controlling neuroblast numbers and proliferation.

Abdomen↗
PubMed1997

Synergy between suppressor of Hairless and Notch in regulation of Enhancer of split m gamma and m delta expression.

The Notch signaling pathway is known to regulate cell fate decisions in a variety of organisms from worms to humans. Although several components of the pathway have been characterized, the actual mechanism and molecular results of signaling remain elusive. We have examined the role of the Notch signaling pathway in the transcriptional regulation of two Drosophila Enhancer of split [E(spl)] genes, whose gene products have been shown to be downstream players in the pathway. Using a reporter assay system in Drosophila tissue culture cells, we have observed a significant induction of E(spl) m gamma and m delta expression after cotransfection with activated Notch. Characterization of the 5' regulatory regions of these two genes led to the identification of a number of target sites for the Suppressor of Hairless [Su(H)] protein, a transcription factor activated by Notch signaling. We show that Notch-inducible expression of E(spl) m gamma and m delta both in cultured cells and in vivo is dependent on functional Su(H). Although overexpression of Su(H) augments the level of induction of the reporter genes by activated Notch, Su(H) alone is insufficient to produce high levels of transcriptional activation. Despite the synergy observed between activated Notch and Su(H), the former affects neither the nuclear localization nor the DNA binding activity of the latter.

Animals↗
PubMed1997

Notch signalling regulates veinlet expression and establishes boundaries between veins and interveins in the Drosophila wing.

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.

Animals↗
PubMed1997

Feed-back mechanisms affecting Notch activation at the dorsoventral boundary in the Drosophila wing.

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.

Animals↗
PubMed1996

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.

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.

Animals↗
PubMed1995

A Drosophila E(spł) gene is "neurogenic" in Xenopus: a green fluorescent protein study.

A Drosophila Enhancer of split [E(spl)] bHLH protein, m delta, was misexpressed in Xenopus embryos along with green fluorescent protein (GFP) as a lineage label. The Drosophila protein translocated to the nucleus of Xenopus cells and led to neural hypertrophy in the GFP-labeled dorsal ectoderm, a phenotype similar to that caused by the misexpression of activated Xotch. Our data indicate a strong conservation in E(spl)bHLH function in the Notch signaling pathway of flies and vertebrates.

Animals↗
PubMed1994

The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo.

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.

Animals↗
PubMed1991

Physical activity patterns defined by continuous heart rate monitoring.

To investigate the physical activity patterns of British primary schoolchildren (mean (SD) 10.7 (0.3) years) the minute by minute heart rates of 67 boys and 65 girls were monitored continuously for three 12 hour periods during normal schooldays. In addition 39 children had their heart rates monitored during a 12 hour period on a Saturday. Few children experienced the volume (frequency, intensity, and duration) of physical activity associated with an improvement in cardiopulmonary fitness. Shorter (five minute) periods of the required intensity were, however, quite common. No difference between moderate amounts of activity was detected between boys and girls, but the boys had more five minute sessions of intense activity than the girls. These findings suggest that more research into the effects of short periods of intense physical activity on the cardiopulmonary systems of young children is required and that the determinants of habitual physical activity require further investigation especially in the context of sex differences at such an early age.

Child↗
PubMed1989

Kainic acid inhibits cholecystokinin release from rat hippocampal slices.

Antagonistic interactions between cholecystokinin (CCK) and nanomolar concentrations of kainic acid (KA) have been reported in area CA3 of the rat hippocampal slice. This study tested the possibility that kainic acid inhibits the release of CCK. Elevated K+ was found to release CCK from hippocampal slices in a Ca2+-dependent manner. KA, at concentrations as low as 100 nM, inhibited this release by about one-third. Because CCK appears to exert a net inhibitory effect on the firing of CA3 pyramidal cells, the epileptogenic action of KA may be explained, in part, by the depression of CCK release.

Animals↗
PubMedDate not supplied

Recovery of polluted ecosystems: the case for long-term studies.

Recovery of marine ecosystems from pollution has tended to receive less attention than the study of new or continuing impacts, but such studies are important in charting recovery from acute incidents and following legislation to deal with chronic contamination. Recovery is inevitably a long-term process, and where such studies have been made they are often too short-lived. Interest quickly wanes following an acute incident and governmental bodies rapidly switch to new legislative priorities for chronic inputs. We review three case studies: recovery of dogwhelk populations after local extinction by tributyl tin leachates from anti-fouling paints; recovery of rocky shore communities from oil spills; and recovery of estuarine ecosystems from industrial and urban development. We then make some generalisations about recovery processes before making a plea for long-term studies of polluted areas.

Animals↗