The Notch locus of Drosophila is required in epidermal cells for epidermal development

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 875-885 ◽  
Author(s):  
P.E. Hoppe ◽  
R.J. Greenspan
Keyword(s):  
Cell Surface ◽  
Cell Fate ◽  
Mitotic Recombination ◽  
Epidermal Cells ◽  
Cell Fate Decisions ◽  
Notch Protein ◽  
Notch Gene ◽  
Cell Surface Interactions ◽  
Notch Locus ◽  
Type Gene

The Notch locus of Drosophila plays an important role in cell fate decisions within the neurogenic ectoderm, a role thought to involve interactions at the cell surface. We have assayed the requirement for Notch gene expression in epidermal cells by two kinds of genetic mosaics. First, with gynandromorphs, we removed the wild-type gene long before the critical developmental events to produce large mutant clones. The genotype of cells in large clones was scored by means of an antibody to the Notch protein. Second, using mitotic recombination, we removed the gene at successively later times after completion of the mitotically active early cleavage stages, to produce small clones. These clones were detected by means of a linked mutation of cuticle pattern, armadillo. The results of both experiments demonstrate a requirement for Notch expression by epidermal cells, and thus argue against the model that the Notch product acts as a signal required only in the neuroblast to influence neighboring epidermal cells. The mitotic recombination experiment revealed that Notch product is required by epidermal cells subsequent to neuroblast delamination. This result implies that the Notch gene functions to maintain the determined state of epidermal cells, possibly by mediating cell surface interactions within the epidermis.

glp-1 can substitute for lin-12 in specifying cell fate decisions in Caenorhabditis elegans

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1019-1027 ◽  
Author(s):  
K. Fitzgerald ◽  
H.A. Wilkinson ◽  
I. Greenwald
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Effector Proteins ◽  
Regulatory Sequences ◽  
Animal Kingdom ◽  
Cell Fate Decisions ◽  
Notch Gene ◽  
Epidermal Growth ◽  
Differential Gene ◽  
Mutant Phenotypes

Members of the lin-12/Notch gene family encode receptors for intercellular signals and are found throughout the animal kingdom. In many animals, the presence of at least two lin-12/Notch genes raises the issue of the significance of this duplication and divergence. In Caenorhabditis elegans, two lin-12/Notch genes, lin-12 and glp-1, encode proteins that are 50% identical, with different numbers of epidermal growth factor-like motifs in their extracellular domains. Many of the cell fate decisions mediated by lin-12 and glp-1 are distinct. Here, we express glp-1 protein under the control of lin-12 regulatory sequences in animals lacking endogenous lin-12 activity and find that glp-1 can substitute for lin-12 in mediating cell fate decisions. These results imply that the lin-12 and glp-1 proteins are biochemically interchangeable, sharing common ligand and effector proteins, and that the discrete lin-12 and glp-1 mutant phenotypes result from differential gene expression. In addition, these results suggest that the duplicate lin-12/Notch genes found in vertebrates may also be biochemically interchangeable.

Notch signaling in pathogenesis of diseases

2014 ◽  
Vol 2 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Christense ME ◽  
Carolan BS
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Gene Polymorphisms ◽  
Fixed Effects ◽  
Vascular System ◽  
Meta Analysis ◽  
Tumor Formation ◽  
Cell Fate Decisions ◽  
Pubmed Database ◽  
Notch Gene

The Notch signaling pathway functions on cell fate decisions in a variety of different organizations in multicellular organisms, such as the hematopoietic system, nervous system, vascular system, skin and pancreas. In the majority of cases, Notch signaling blocks cell differentiation towards a primary process, and instead, direct them to a second differentiation. Altering the differentiation program or forcing it to remain in the undifferentiated state, there are several human diseases linked to defects in genes involved in Notch signaling, aberrant Notch signaling has been observed in a number of human cancers, suggesting a possible role of Notch signaling in tumor formation. Further, Recent study demonstrated an essential role for Notch1 in the corneal epithelial barrier recovery after wounding. We systematically searched the electronic PubMed database for research articles about Notch gene polymorphisms and diseases up to October 2013. Revman 5.0 software was adopted to conduct the meta-analysis. Crude odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated by either fixed-effects model or random-effects model. The present meta-analysis suggests that Notch gene polymorphisms are associated with the susceptibility of many diseases especially cancer.

Notch signaling in pathogenesis of diseases

2014 ◽  
Vol 2 (1) ◽  
pp. 1-4
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Gene Polymorphisms ◽  
Fixed Effects ◽  
Vascular System ◽  
Meta Analysis ◽  
Tumor Formation ◽  
Cell Fate Decisions ◽  
Pubmed Database ◽  
Notch Gene

The Notch signaling pathway functions on cell fate decisions in a variety of different organizations in multicellular organisms, such as the hematopoietic system, nervous system, vascular system, skin and pancreas. In the majority of cases, Notch signaling blocks cell differentiation towards a primary process, and instead, direct them to a second differentiation. Altering the differentiation program or forcing it to remain in the undifferentiated state, there are several human diseases linked to defects in genes involved in Notch signaling, aberrant Notch signaling has been observed in a number of human cancers, suggesting a possible role of Notch signaling in tumor formation. Further, Recent study demonstrated an essential role for Notch1 in the corneal epithelial barrier recovery after wounding. We systematically searched the electronic PubMed database for research articles about Notch gene polymorphisms and diseases up to October 2013. Revman 5.0 software was adopted to conduct the meta-analysis. Crude odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated by either fixed-effects model or random-effects model. The present meta-analysis suggests that Notch gene polymorphisms are associated with the susceptibility of many diseases especially cancer.

scholarly journals Internalization of B Cell Receptors in Human EU12μHC+Immature B Cells Specifically Alters Downstream Signaling Events

2013 ◽  
Vol 2013 ◽  
pp. 1-9
Author(s):  
Jing Liu ◽  
Wanqin Xie ◽  
Miles D. Lange ◽  
Sang Yong Hong ◽  
Kaihong Su ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Fate ◽  
Cell Activation ◽  
Underlying Mechanism ◽  
Cell Fate Decisions ◽  
Downstream Signaling ◽  
Signaling Events ◽  
Immature B Cells

It has been recognized for a long time that engagement of B cell antigen receptors (BCRs) on immature B cells or mature B cells leads to completely opposite cell fate decisions. The underlying mechanism remains unclear. Here, we show that crosslinking of BCRs on human EU12μHC+immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12μHC+cells showed impaired Ca2+flux, delayed SYK phosphorylation, and decreased CD19 and FOXO1 phosphorylation, which differ from those in mature Daudi or Ramos B cells with partial internalization of BCRs. In contrast, sustained phosphorylation and reactivation of ERK upon restimulation were observed in the EU12μHC+cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12μHC+cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation.

scholarly journals Evidence that Mycobacterial PE_PGRS Proteins Are Cell Surface Constituents That Influence Interactions with Other Cells

2001 ◽  
Vol 69 (12) ◽  
pp. 7326-7333 ◽  
Author(s):  
Michael J. Brennan ◽  
Giovanni Delogu ◽  
Yiping Chen ◽  
Stoyan Bardarov ◽  
Jordan Kriakov ◽  
...  
Keyword(s):  
Cell Surface ◽  
Liquid Medium ◽  
Genomic Sequence ◽  
Wild Type ◽  
Phenotypic Properties ◽  
Transposon Insertion ◽  
Cell Surface Interactions ◽  
Type Gene ◽  
Aggregative Growth ◽  
Related Proteins

ABSTRACT The elucidation of the genomic sequence of Mycobacterium tuberculosis revealed the presence of a novel multigene family designated PE/PE_PGRS that encodes numerous, highly related proteins of unknown function. In this study, we demonstrate that a transposon insertion in a PE_PGRS gene (1818PE_PGRS) found inMycobacterium bovis BCG Pasteur, which is the BCG homologue of the M. tuberculosis H37Rv gene Rv1818c, introduces new phenotypic properties to this BCG strain. These properties include dispersed growth in liquid medium and reduced infection of macrophages. Complementation of the 1818PE_PGRS::Tn5367 mutant with the wild-type gene restores both aggregative growth (clumping) in liquid medium and reestablishes infectivity of macrophages to levels equivalent to those for the parent BCG strain. Western blot analysis using antisera raised against the 1818PE_PGRS protein shows that PE_PGRS proteins are found in cell lysates of BCG andM. tuberculosis H37Ra and in the cell wall fraction of M. tuberculosis H37Rv. Moreover, immunofluorescent labeling of mycobacteria indicates that certain PE_PGRS proteins are localized at the cell surface of BCG andM. tuberculosis. Together these results suggest that certain PE_PGRS proteins may be found at the surface of mycobacteria and influence both cell surface interactions among mycobacteria as well as the interactions of mycobacteria with macrophages.

scholarly journals Expression of constitutively active Notch arrests follicle cells at a precursor stage during Drosophila oogenesis and disrupts the anterior-posterior axis of the oocyte

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3639-3650 ◽  
Author(s):  
M.K. Larkin ◽  
K. Holder ◽  
C. Yost ◽  
E. Giniger ◽  
H. Ruohola-Baker
Keyword(s):  
Cell Fate ◽  
Ovarian Follicle ◽  
Follicle Cells ◽  
Cell Fates ◽  
Drosophila Oogenesis ◽  
Cell Fate Decisions ◽  
Notch Gene ◽  
Anterior Posterior ◽  
Anterior Posterior Axis ◽  
Constitutively Active

During early development, there are numerous instances where a bipotent progenitor divides to give rise to two progeny cells with different fates. The Notch gene of Drosophila and its homologues in other metazoans have been implicated in many of these cell fate decisions. It has been argued that the role of Notch in such instances may be to maintain cells in a precursor state susceptible to specific differentiating signals. This has been difficult to prove, however, due to a lack of definitive markers for precursor identity. We here perform molecular and morphological analyses of the roles of Notch in ovarian follicle cells during Drosophila oogenesis. These studies show directly that constitutively active Notch arrests cells at a precursor stage, while the loss of Notch function eliminates this stage. Expression of moderate levels of activated Notch leads to partial transformation of cell fates, as found in other systems, and we show that this milder phenotype correlates with a prolonged, but still transient, precursor stage. We also find that expression of constitutively active Notch in follicle cells at later stages leads to a defect in the anterior-posterior axis of the oocyte.

scholarly journals A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2057-2062 ◽  
Author(s):  
LA Milner ◽  
R Kopan ◽  
DI Martin ◽  
ID Bernstein
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Amino Acid Sequences ◽  
Cell Fate Decisions ◽  
Reverse Transcription Pcr ◽  
Cd34 Cells ◽  
Pcr Products ◽  
Notch Gene ◽  
Mediate Cell ◽  
Notch Homologue

Members of the Notch gene family have been shown to mediate cell-fate decisions by multipotent precursors in a number of different systems. To determine whether members of this family might play a similar role in hematopoiesis, we asked if homologues of the Notch gene are expressed in human hematopoietic precursors. Using degenerate oligonucleotides corresponding to conserved amino acid sequences in known Notch homologues as primers for the polymerase chain reaction (PCR), we demonstrated that at least one Notch homologue is expressed in human bone marrow CD34+ cells, a population enriched for hematopoietic precursors. Cloning and sequencing of the PCR products identified this Notch homologue as TAN-1, a member of the Notch family previously cloned from a T-cell leukemia with a translocation involving this gene. Subsequent evaluation of bone marrow hematopoietic cells for TAN-1 expression using a reverse transcription-PCR assay confirmed the expression of TAN-1 in CD34+ hematopoietic precursors, including the immature subset that lacks expression of lineage-associated antigens (CD34+lin-). These findings, together with the known role of Notch homologues in other systems, suggest that members of the Notch family, including TAN-1, may be involved in mediating cell-fate decisions during hematopoiesis.

Notch2: a second mammalian Notch gene

Development ◽  
1992 ◽  
Vol 116 (4) ◽  
pp. 931-941 ◽  
Author(s):  
G. Weinmaster ◽  
V.J. Roberts ◽  
G. Lemke
Keyword(s):  
Cell Fate ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Cell Surface Receptor ◽  
Cellular Interactions ◽  
Spatial And Temporal Patterns ◽  
Cell Fate Decisions ◽  
Adult Rat ◽  
Surface Receptor ◽  
Notch Gene

Notch is a cell surface receptor that mediates a wide variety of cellular interactions that specify cell fate during Drosophila development. Recently, homologs of Drosophila Notch have been isolated from Xenopus, human and rat, and the expression patterns of these vertebrate proteins suggest that they may be functionally analogous to their Drosophila counterpart. We have now identified a second rat gene that exhibits substantial nucleic and amino acid sequence identity to Drosophila Notch. This gene, designated Notch2, encodes a protein that contains all the structural motifs characteristic of a Notch protein. Thus, mammals differ from Drosophila in having more than one Notch gene. Northern and in situ hybridisation analyses in the developing and adult rat identify distinct spatial and temporal patterns of expression for Notch1 and Notch2, indicating that these genes are not redundant. These results suggest that the great diversity of cell-fate decisions regulated by Notch in Drosophila may be further expanded in vertebrates by the activation of distinct Notch proteins.

scholarly journals A genetic analysis of deltex and its interaction with the Notch locus in Drosophila melanogaster.

Genetics ◽  
1992 ◽  
Vol 131 (1) ◽  
pp. 99-112 ◽  
Author(s):  
M J Gorman ◽  
J R Girton
Keyword(s):  
Cell Fate ◽  
Developmental Pathways ◽  
Phenotypic Characterization ◽  
Loss Of Function ◽  
Cell Fates ◽  
Cone Cells ◽  
Notch Gene ◽  
Notch Locus ◽  
Fate Decision

Abstract During Drosophila development networks of genes control the developmental pathways that specify cell fates. The Notch gene is a well characterized member of some cell fate pathways, and several other genes belonging to these same pathways have been identified because they share a neurogenic null phenotype with Notch. However, it is unlikely that the neurogenic genes represent all of the genes in these pathways. The goal of this research was to use a genetic approach to identify and characterize one of the other genes that acts with Notch to specify cell fate. Mutant alleles of genes in the same pathway should have phenotypes similar to Notch alleles and should show phenotypic interactions with Notch alleles. With this approach we identified the deltex gene as a potential cell fate gene. An extensive phenotypic characterization of loss-of-function deltex phenotypes showed abnormalities (such as thick wing veins, double bristles and extra cone cells) that suggest that deltex is involved in cell fate decision processes. Phenotypic interactions between deltex and Notch as seen in double mutants showed that Notch and deltex do not code for duplicate functions and that the two genes function together in many different developing tissues. The results of these investigations lead to the conclusion that the deltex gene functions with the Notch gene in one or more developmental pathways to specify cell fate.

scholarly journals Modifications of the notch function by Abruptex mutations in Drosophila melanogaster.

Genetics ◽  
1994 ◽  
Vol 136 (1) ◽  
pp. 183-194 ◽  
Author(s):  
J F de Celis ◽  
A Garcia-Bellido
Keyword(s):  
Transmembrane Protein ◽  
Extracellular Domain ◽  
Cell Fates ◽  
Notch Protein ◽  
Protein Functions ◽  
Notch Gene ◽  
Epidermal Growth ◽  
Notch Locus ◽  
Notch Ligands ◽  
Notch Activation

Abstract The function of the Notch gene is required in cell interactions defining alternative cell fates in several developmental processes. The Notch gene encodes a transmembrane protein with 36 epidermal growth factor (EGF)-like repeats in its extracellular domain. This protein functions as a receptor that interacts with other transmembrane proteins, such as Serrate and Delta, which also have EGF repeats in their extracellular domain. The Abruptex mutations of the Notch locus are associated with amino acid substitutions in the EGF repeats 24-29 of the Notch protein. We have studied, in genetic combinations, the modifications of Notch function caused by Abruptex mutations. These mutations lead to phenotypes which are opposite to those caused by Notch deletions. The Abruptex phenotypes are modified by the presence of mutations in other loci, in particular in the genes Serrate and Delta as well as Hairless, and groucho. The results suggest that all Abruptex mutations cause stronger than normal Notch activation by the Delta protein. Some Abruptex alleles also display an insufficiency of N function. Abruptex alleles which produce stronger enhancement of Notch activation also display stronger Notch insufficiency. This insufficiency could be due to reduced ability of Abruptex proteins to interact with Notch ligands and/or to form functional Notch dimers.

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