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At least 1,603 records · Page 89Linked to original sources
PubMed1997

The repair of UV-induced cyclobutane pyrimidine dimers in the individual genes Gart, Notch and white from isolated brain tissue of Drosophila melanogaster.

We have measured the induction and removal of UV-induced cyclobutane pyrimidine dimers from defined, DNA sequences in brains isolated from wild-type Drosophila melanogaster third instar larvae. Brains were exposed to a single dose of 500 J/m2 UVB and kept in the dark for up to 48 h. Within 48 h after irradiation, 50% of the dimers are removed from the actively transcribed genes Gart and Notch. Moreover, these kinetics are similar to the time course of dimer removal measured in the transcriptionally inactive white gene. It is further demonstrated that the genome overall is repaired at a similar rate. The results are discussed with respect to the in vivo irradiation of brains and to the data found for gene-specific repair in other eukaryotes.

ATP-Binding Cassette Transporters↗
PubMed2001

Spatial regulation of DELTA expression mediates NOTCH signalling for segmentation of Drosophila legs.

The Notch (N) signalling pathway is recruited for segregation of cell fates in a number of Drosophila tissue types. We show here that N dependent segmentation of Drosophila legs is regulated by a dynamic pattern of expression of its ligand, DELTA (DL). During third larval instar and early stages of pupation, high levels of DL expression is seen in stripes of cells in the leg imaginal discs which later form the proximal borders of leg joints. These domains also displayed heightened Dl enhancer activity. During subsequent stages of pupation, following segmentation of the leg primordium, DL expression becomes uniform throughout these segments barring the joints. We further show that regulatory Dl mutations or mis-expression of DL abolish leg segmentation. Domains of N signalling for segmentation of legs of flies are thus set up by a stringent spatial regulation of expression of its ligand at the segment border. Further, a comparable role of DL in antennal development reveals a common paradigm of DL-N signalling for segmentation of appendages in flies.

Animals↗
PubMed2002

Furin cleavage is not a requirement for Drosophila Notch function.

Notch (N) is a large transmembrane protein that acts as a receptor in an evolutionarily conserved intercellular signalling pathway. Because of this conservation, it has been assumed that biochemical events mediating N function are identical in all species. For instance, intracellular maturation by furin protease and subunit assembly leading to the formation of a heterodimeric cell surface N receptor are thought to be central to its function in both mammals and flies. However, in Drosophila the majority of N appears to be full-length. It has not been determined whether this full-length N protein is on the cell surface. We describe experiments which indicate that unlike mammalian N, the majority of Drosophila N on the cell surface is full-length and that in Drosophila, in vivo, furin cleavage is not required for biological activity. We further show that the behaviour of fly and mouse N can be interchanged simply by swapping the regions in which the mammalian furin-like cleavage site is located.

Amino Acid Sequence↗
PubMed2003

Vein-positioning in the Drosophila wing in response to Hh; new roles of Notch signaling.

The Drosophila wing is a classical model for studying the generation of developmental patterns. Previous studies have suggested that vein primordia form at boundaries between discrete sectors of gene expression along the antero-posterior (A/P) axis in the larval wing imaginal disc. Observation that the vein marker rhomboid (rho) is expressed at the centre of wider vein-competent domains led to propose that narrow vein primordia form first, and produce secondary short-range signals activating provein genes in neighbouring cells (see Curr. Opin. Genet. Dev. 10 (2000) 393). Here, we examined how the central L3 and L4 veins are positioned relative to the limits of expression of Collier (Col), a dose-dependent Hedgehog (Hh) target activated in the wing A/P organiser. We found that rho expression is first activated in broad domains adjacent to Col-expressing cells and secondarily restricted to the centre of these domains. This restriction which depends upon Notch (N) signaling sets the L3 and L4 vein primordia off the boundaries of Col expression. N activity is also required to fix the anterior limit of Col expression by locally antagonising Hh activation, thus precisely positioning the L3 vein primordium relative to the A/P compartment boundary. Experiments using Nts mutants further indicated that these two activities of N could be temporally uncoupled. Together, these observations highlight new roles of N in topologically linking the position of veins to prepattern gene expression.

Animals↗
PubMed1997

Notch signalling in development: on equivalence groups and asymmetric developmental potential.

Notch-mediated lateral signalling takes place between equivalent cells that then adopt alternative fates. An example is the epidermal-neural choice in the Drosophila neuro-ectoderm. Sometimes this choice is random. Sometimes it is biased to a preferred cell by an extrinsic signal. Sometimes the neural precursor is predetermined. A stochastic outcome is probably older in evolutionary terms.

Animals↗
PubMed1999

Notch around the clock.

The establishment of a segmental pattern within the vertebrate body plan is achieved during embryogenesis by the somitogenesis process. Two molecular systems have been implicated in this phenomenon: a molecular clock linked to vertebrate segmentation and the Notch signalling pathway. Rhythmic expression of the Lunatic Fringe gene in the presomitic mesoderm has now provided a link between these two systems.

Animals↗
PubMedDate not supplied

The scabrous protein can act as an extracellular antagonist of notch signaling in the Drosophila wing.

Notch (N) is a receptor for signals that inhibit neural precursor specification [1-6]. As N and its ligand Delta (DI) are expressed homogeneously, other molecules may be differentially expressed or active to permit neural precursor cells to arise intermingled with nonneural cells [7,8]. During Drosophila wing development, the glycosyltransferase encoded by the gene fringe (fng) promotes N signaling in response to DI, but inhibits N signaling in response to Serrate (Ser), which encodes a ligand that is structurally similar to DI. Dorsal expression of Fng protein localizes N signaling to the dorsoventral (DV) wing margin [9-11]. The secreted protein Scabrous (Sca) is a candidate for modulation of N in neural cells. Mutations at the scabrous (sca) locus alter the locations where precursor cells form in the peripheral nervous system [12,13]. Unlike fringe, sca mutations act cell non-autonomously [12]. Here, we report that targeted misexpression of Sca during wing development inhibited N signaling, blocking expression of all N target genes. Sca reduced N activation in response to DI more than in response to Ser. Ligand-independent signaling by overexpression of N protein, or by expression of activated truncated N molecules, was not inhibited by Sca. Our results indicate that Sca can act on N to reduce its availability for paracrine and autocrine interactions with DI and Ser, and can act as an antagonist of N signaling.

Animals↗
PubMed2002

Notch cleavage: Nicastrin helps Presenilin make the final cut.

Presenilin is thought to be the proteolytic component of gamma-secretase, responsible for the intramembranous cleavage of substrates that include the activated Notch receptor. Recent studies have identified the novel protein Nicastrin as another essential component of the Presenilin/gamma-secretase complex.

Amyloid Precursor Protein Secretases↗
PubMed2003

Notch signaling: endocytosis makes delta signal better.

Endocytosis of cell surface receptors is involved in down-regulation of receptor activity. Recent findings indicate that, paradoxically, endocytosis of a membrane-spanning ligand may up-regulate receptor activity: the zebrafish E3 ligase Mind bomb promotes the endocytosis of Delta and is required for efficient activation of Notch.

Animals↗
PubMed1997

T-call development: is notch a key player in lineage decisions?

At two consecutive 'checkpoints' in their development, T cells have to be rescued from programmed cell death and to choose between distinct lineage fates; recent results show that the Notch transmembrane receptor can significantly influence T-cell development at both of these points.

Animals↗
PubMed1997

Developmental signaling: notch signals Kuz it's cleaved.

Recent experiments with Kuzbanian, a disintegrin metalloprotease that is required during development for lateral inhibitory signaling, suggest that signaling molecules of the Notch family may guide cell fate only after they are activated by proteolysis, and that the proteolysis may be catalyzed by Kuzbanian.

Disintegrins↗
PubMed1998

Vertebrate segmentation: the clock is linked to Notch signalling.

The periodic formation of somites during vertebrate segmentation has been suggested to involve a molecular 'segmentation clock'. Recent observations of cyclic Lunatic fringe expression in chick and mouse embryos link the segmentation clock to Delta-Notch signalling.

Animals↗
PubMed1999

Eye development: Notch lends a handedness.

The arrangement of photoreceptors in the ommatidia of the Drosophila compound eye is polarized, having a handedness or chirality. Notch signalling helps determine this handedness, first by establishing a signalling center at the eye equator, and second by mediating a choice between two photoreceptor fates

Animals↗
PubMed2003

Notch3, another Notch in T cell development.

Different members of the Notch family have been described to play a critical role in T cell lineage commitment and T cell development and functions. Nevertheless, whether they act as redundant molecules, by affecting the same molecular mechanisms, or play distinct roles in T cell differentiation and/or functions is not clear. Altered Notch3 signaling impairs the developmentally regulated interplay between pre-TCR and NF-kappaB signaling and allows the disruption of early thymocyte differentiation and the development of T cell leukemia, thus identifying the crucial role of Notch3 receptor in the coordination of T cell differentiation and growth control.

Animals↗
PubMed1999

Notch signaling is not sufficient to define the affinity boundary between dorsal and ventral compartments.

The developing limbs of Drosophila are subdivided into distinct cells populations known as compartments. Short-range interaction between cells in adjacent compartments induces expression of signaling molecules at the compartment boundaries. In addition to serving as the sources of long-range signals, compartment boundaries prevent mixing of the adjacent cell populations. One model for boundary formation proposes that affinity differences between compartments are defined autonomously as one aspect of compartment-specific cell identity. An alternative is that the affinity boundary depends on signaling between compartments. Here, we present evidence that the dorsal selector gene apterous plays a role in establishing the dorsoventral affinity boundary that is independent of Notch-mediated signaling between dorsal and ventral cells.

Animals↗
PubMed2003

A mutant form of MeCP2 protein associated with human Rett syndrome cannot be displaced from methylated DNA by notch in Xenopus embryos.

MeCP2 is a DNA binding protein that represses transcription of methylated genes in vitro, but the endogenous function of MeCP2 in vivo is unclear. Here, we demonstrate that in Xenopus laevis embryos MeCP2 is a partner of the SMRT corepressor complex that regulates the expression of a neuronal repressor xHairy2a in differentiating neuroectoderm. The MeCP2/SMRT complex is bound to the promoter of the silenced xHairy2a gene and is displaced upon activation by the Notch intracellular domain (NICD). A truncated form of MeCP2 (R168X) found in patients with Rett syndrome cannot interact with the SMRT complex or fully activate xHairy2a during primary neurogenesis. This disruption of MeCP2 activity results in abnormal patterning of primary neurons during neuronal differentiation. Our results support a model whereby the dynamic association of MeCP2 with methylated DNA and the SMRT complex regulates a gene involved in cell fate decisions during primary neurogenesis in Xenopus.

Animals↗
PubMed2000

Does dysregulation of the Notch and wingless/Wnt pathways underlie the pathogenesis of Alzheimer's disease?

Alzheimer's disease is characterized by the presence of neurofibrillary tangles and senile neuritic plaques in the brain. Tangles are aggregates of paired helical filaments composed of the microtubule-associated protein, tau, in a hyperphosphorylated state. Senile plaques have a core of amyloid beta-peptide derived by proteolysis of the amyloid precursor protein. A major hurdle in defining the pathogenic mechanisms in Alzheimer's disease is to understand how both amyloid beta-peptide deposition and paired helical filament formation are biochemically linked. Recent genetic discoveries provide some clues, suggesting that components of two developmentally important signalling pathways, Notch and wingless, or the vertebrate homologue of wingless, Wnt, are involved.

Alzheimer Disease↗