scholarly journals Expression of Notch 1, 2 and 3 is regulated by epithelial-mesenchymal interactions and retinoic acid in the developing mouse tooth and associated with determination of ameloblast cell fate.

1995 ◽  
Vol 130 (2) ◽  
pp. 407-418 ◽  
Author(s):  
T A Mitsiadis ◽  
M Lardelli ◽  
U Lendahl ◽  
I Thesleff
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Transmembrane Protein ◽  
Biological Effects ◽  
Expression Patterns ◽  
Notch 1 ◽  
Cell Fate Decisions ◽  
Notch Gene ◽  
Dental Epithelium

Notch 1, Notch 2, and Notch 3 are three highly conserved mammalian homologues of the Drosophila Notch gene, which encodes a transmembrane protein important for various cell fate decisions during development. Little is yet known about regulation of mammalian Notch gene expression, and this issue has been addressed in the developing rodent tooth during normal morphogenesis and after experimental manipulation. Notch 1, 2, and 3 genes show distinct cell-type specific expression patterns. Most notably, Notch expression is absent in epithelial cells in close contact with mesenchyme, which may be important for acquisition of the ameloblast fate. This reveals a previously unknown prepatterning of dental epithelium at early stages, and suggests that mesenchyme negatively regulates Notch expression in epithelium. This hypothesis has been tested in homo- and heterotypic explant experiments in vitro. The data show that Notch expression is downregulated in dental epithelial cells juxtaposed to mesenchyme, indicating that dental epithelium needs a mesenchyme-derived signal in order to maintain the downregulation of Notch. Finally, Notch expression in dental mesenchyme is upregulated in a region surrounding beads soaked in retinoic acid (50-100 micrograms/ml) but not in fibroblast growth factor-2 (100-250 micrograms/ml). The response to retinoic acid was seen in explants of 11-12-d old mouse embryos but not in older embryos. These data suggest that Notch genes may be involved in mediating some of the biological effects of retinoic acid during normal development and after teratogenic exposure.

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.

Overexpression of lunatic fringe does not affect epithelial cell differentiation in the developing mouse lung

2005 ◽  
Vol 288 (4) ◽  
pp. L672-L682 ◽  
Author(s):  
Minke van Tuyl ◽  
Freek Groenman ◽  
Maciek Kuliszewski ◽  
Ross Ridsdale ◽  
Jinxia Wang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Expression Patterns ◽  
Neuroendocrine Cells ◽  
Mouse Lung ◽  
Cell Fate Decisions ◽  
Lunatic Fringe ◽  
Hes1 Expression

The Notch/Notch-ligand pathway regulates cell fate decisions and patterning in various tissues. Several of its components are expressed in the developing lung, suggesting that this pathway is important for airway cellular patterning. Fringe proteins, which modulate Notch signaling, are crucial for defining morphogenic borders in several organs. Their role in controlling cellular differentiation along anterior-posterior axis of the airways is unknown. Herein, we report the temporal-spatial expression patterns of Lunatic fringe (Lfng) and Notch-regulated basic helix-loop-helix factors, Hes1 and Mash-1, during murine lung development. Lfng was only expressed during early development in epithelial cells lining the larger airways. Those epithelial cells also expressed Hes1, but at later gestation Hes1 expression was confined to epithelium lining the terminal bronchioles. Mash-1 displayed a very characteristic expression pattern. It followed neural crest migration in the early lung, whereas at later stages Mash-1 was expressed in lung neuroendocrine cells. To clarify whether Lfng influences airway cell differentiation, Lfng was overexpressed in distal epithelial cells of the developing mouse lung. Overexpression of Lfng did not affect spatial or temporal expression of Hes1 and Mash-1. Neuroendocrine CGRP and protein gene product 9.5 expression was not altered by Lfng overexpression. Expression of proximal ciliated (β-tubulin IV), nonciliated ( CCSP), and distal epithelial cell ( SP-C, T1α) markers also was not influenced by Lfng excess. Overexpression of Lfng had no effect on mesenchymal cell marker (α-sma, vWF, PECAM-1) expression. Collectively, the data suggest that Lunatic fringe does not play a significant role in determining cell fate in fetal airway epithelium.

Mouse Serrate-1 (Jagged-1): expression in the developing tooth is regulated by epithelial-mesenchymal interactions and fibroblast growth factor-4

Development ◽  
1997 ◽  
Vol 124 (8) ◽  
pp. 1473-1483 ◽  
Author(s):  
T.A. Mitsiadis ◽  
D. Henrique ◽  
I. Thesleff ◽  
U. Lendahl
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cell Fate ◽  
Tooth Development ◽  
Expression Patterns ◽  
Control Cell ◽  
Fibroblast Growth ◽  
Down Regulation ◽  
Cell Fate Decisions ◽  
Dental Epithelium

Serrate-like genes encode transmembrane ligands to Notch receptors and control cell fate decisions during development. In this report, we analyse the regulation of the mouse Serrate-1 gene during embryogenesis. The Serrate-1 gene is expressed from embryonic day 7.5 (E7.5) and expression is often observed at sites of epithelial-mesenchymal interactions, including the developing tooth, where Serrate-1 is first (E11.5) expressed in all cells of the dental epithelium, but not in mesenchyme. A transient upregulation in dental mesenchyme (E12.5-15.5) is correlated with down-regulation of Serrate-1 expression in epithelial cells contacting the mesenchyme, i.e. in the cells destined to become ameloblasts. This expression pattern is reproduced in explants of dental epithelium and mesenchyme in vitro: epithelium induces Serrate-1 expression in mesenchyme, while epithelium in close proximity to this mesenchyme does not express detectable levels of Serrate-1 mRNA, suggesting that down-regulation of Serrate-1 expression in preameloblasts is caused by mesenchyme-derived signals. Finally, regulation of Serrate-1 expression differs from that of Notch genes. The Serrate-1 gene is induced in dental mesenchyme by fibroblast growth factor-4, but not by bone morphogenetic proteins, while the converse is true for Notch genes. This indicates that, at least during tooth development, the expression patterns observed for receptors and ligands in the Notch signaling pathway are generated by different induction mechanisms.

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.

scholarly journals Estrogen Signaling Drives Ciliogenesis in Human Endometrial Organoids

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2282-2297 ◽  
Author(s):  
Sandra Haider ◽  
Magdalena Gamperl ◽  
Thomas R Burkard ◽  
Victoria Kunihs ◽  
Ulrich Kaindl ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Expression Patterns ◽  
Estrogen Signaling ◽  
Ciliated Cells ◽  
Cell Fate Decisions ◽  
Primary Driver ◽  
Endometrial Epithelium ◽  
Cyclic Changes

Abstract The human endometrium is the inner lining of the uterus consisting of stromal and epithelial (secretory and ciliated) cells. It undergoes a hormonally regulated monthly cycle of growth, differentiation, and desquamation. However, how these cyclic changes control the balance between secretory and ciliated cells remains unclear. Here, we established endometrial organoids to investigate the estrogen (E2)-driven control of cell fate decisions in human endometrial epithelium. We demonstrate that they preserve the structure, expression patterns, secretory properties, and E2 responsiveness of their tissue of origin. Next, we show that the induction of ciliated cells is orchestrated by the coordinated action of E2 and NOTCH signaling. Although E2 is the primary driver, inhibition of NOTCH signaling provides a permissive environment. However, inhibition of NOTCH alone is not sufficient to trigger ciliogenesis. Overall, we provide insights into endometrial biology and propose endometrial organoids as a robust and powerful model for studying ciliogenesis in vitro.

scholarly journals Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels

2008 ◽  
Vol 28 (21) ◽  
pp. 6668-6680 ◽  
Author(s):  
Albertus T. J. Wierenga ◽  
Edo Vellenga ◽  
Jan Jacob Schuringa
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Target Genes ◽  
Expression Patterns ◽  
Activity Levels ◽  
Dependent Manner ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions

ABSTRACT The level of transcription factor activity critically regulates cell fate decisions, such as hematopoietic stem cell (HSC) self-renewal and differentiation. We introduced STAT5A transcriptional activity into human HSCs/progenitor cells in a dose-dependent manner by overexpression of a tamoxifen-inducible STAT5A(1*6)-estrogen receptor fusion protein. Induction of STAT5A activity in CD34+ cells resulted in impaired myelopoiesis and induction of erythropoiesis, which was most pronounced at the highest STAT5A transactivation levels. In contrast, intermediate STAT5A activity levels resulted in the most pronounced proliferative advantage of CD34+ cells. This coincided with increased cobblestone area-forming cell and long-term-culture-initiating cell frequencies, which were predominantly elevated at intermediate STAT5A activity levels but not at high STAT5A levels. Self-renewal of progenitors was addressed by serial replating of CFU, and only progenitors containing intermediate STAT5A activity levels contained self-renewal capacity. By extensive gene expression profiling we could identify gene expression patterns of STAT5 target genes that predominantly associated with a self-renewal and long-term expansion phenotype versus those that identified a predominant differentiation phenotype.

Differential expression of Notch component and effector genes during ovarian follicle and corpus luteum development during the oestrous cycle

2015 ◽  
Vol 27 (7) ◽  
pp. 1038 ◽  
Author(s):  
D. Murta ◽  
M. Batista ◽  
E. Silva ◽  
A. Trindade ◽  
L. Mateus ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Cell Fate ◽  
Ovarian Follicle ◽  
Expression Patterns ◽  
Cell Signalling ◽  
Cell Communication ◽  
Oestrous Cycle ◽  
Specific Expression ◽  
Cell Fate Decisions ◽  
Effector Genes

Ovarian dynamics throughout the female oestrous cycle (EC) are characterised by cyclical follicle and corpus luteum (CL) development. These events are tightly regulated, involving extensive cell-to-cell communication. Notch is an evolutionarily well conserved cell-signalling pathway implicated in cell-fate decisions in several tissues. Here, we evaluated the extra-vascular expression patterns of Notch component and effector genes during follicle and CL development throughout the EC. Five mature CD1 female mice were killed at each EC stage. Blood samples were collected for progesterone measurement, ovaries were processed for immunohistochemistry and expression patterns of Notch components (Notch1, 2 and 3, Jagged1 and Delta-like1 and 4) and effectors (Hes1, Hes2 and Hes5) were characterised. Nuclear detection of Notch effectors indicates that Notch signalling is active in the ovary. Notch components and effectors are differentially expressed during follicle and CL development throughout the EC. The spatial and temporal specific expression patterns are associated with follicle growth, selection and ovulation or atresia and CL development and regression.

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.

Dynamics of Notch signalling in the mouse oviduct and uterus during the oestrous cycle

2016 ◽  
Vol 28 (11) ◽  
pp. 1663 ◽  
Author(s):  
D. Murta ◽  
M. Batista ◽  
A. Trindade ◽  
E. Silva ◽  
L. Mateus ◽  
...  
Keyword(s):  
Real Time ◽  
Cell Fate ◽  
Expression Patterns ◽  
Cell Signalling ◽  
Notch Signalling ◽  
Notch Receptor ◽  
Effector Proteins ◽  
Oestrous Cycle ◽  
Cell Fate Decisions ◽  
Effector Genes

The oviduct and uterus undergo extensive cellular remodelling during the oestrous cycle, requiring finely tuned intercellular communication. Notch is an evolutionarily conserved cell signalling pathway implicated in cell fate decisions in several tissues. In the present study we evaluated the quantitative real-time polymerase chain reaction (real-time qPCR) and expression (immunohistochemistry) patterns of Notch components (Notch1–4, Delta-like 1 (Dll1), Delta-like 4 (Dll4), Jagged1–2) and effector (hairy/enhancer of split (Hes) 1–2, Hes5 and Notch-Regulated Ankyrin Repeat-Containing Protein (Nrarp)) genes in the mouse oviduct and uterus throughout the oestrous cycle. Notch genes are differentially transcribed and expressed in the mouse oviduct and uterus throughout the oestrous cycle. The correlated transcription levels of Notch components and effector genes, and the nuclear detection of Notch effector proteins, indicate that Notch signalling is active. The correlation between transcription levels of Notch genes and progesterone concentrations, and the association between expression of Notch proteins and progesterone receptor (PR) activation, indicate direct progesterone regulation of Notch signalling. The expression patterns of Notch proteins are spatially and temporally specific, resulting in unique expression combinations of Notch receptor, ligand and effector genes in the oviduct luminal epithelium, uterus luminal and glandular epithelia and uterine stroma throughout the oestrous cycle. Together, the results of the present study imply a regulatory role for Notch signalling in oviduct and uterine cellular remodelling occurring throughout the oestrous cycle.

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