scholarly journals Post-Developmental Roles of Notch Signaling in the Nervous System

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 985
Author(s):  
Jose L. Salazar ◽  
Sheng-An Yang ◽  
Shinya Yamamoto
Keyword(s):  
Nervous System ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Fruit Fly ◽  
Notch Signaling Pathway ◽  
Nervous System Development ◽  
Model Organisms ◽  
Cellular Models

Since its discovery in Drosophila, the Notch signaling pathway has been studied in numerous developmental contexts in diverse multicellular organisms. The role of Notch signaling in nervous system development has been extensively investigated by numerous scientists, partially because many of the core Notch signaling components were initially identified through their dramatic ‘neurogenic’ phenotype of developing fruit fly embryos. Components of the Notch signaling pathway continue to be expressed in mature neurons and glia cells, which is suggestive of a role in the post-developmental nervous system. The Notch pathway has been, so far, implicated in learning and memory, social behavior, addiction, and other complex behaviors using genetic model organisms including Drosophila and mice. Additionally, Notch signaling has been shown to play a modulatory role in several neurodegenerative disease model animals and in mediating neural toxicity of several environmental factors. In this paper, we summarize the knowledge pertaining to the post-developmental roles of Notch signaling in the nervous system with a focus on discoveries made using the fruit fly as a model system as well as relevant studies in C elegans, mouse, rat, and cellular models. Since components of this pathway have been implicated in the pathogenesis of numerous psychiatric and neurodegenerative disorders in human, understanding the role of Notch signaling in the mature brain using model organisms will likely provide novel insights into the mechanisms underlying these diseases.

Association between Notch signaling pathway and cancer

2013 ◽  
Vol 19 (4) ◽  
pp. 427-437
Author(s):  
Nadežda Lachej ◽  
Janina Didžiapetrienė ◽  
Birutė Kazbarienė ◽  
Daiva Kanopienė ◽  
Violeta Jonušienė
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Treatment Method ◽  
Notch Signaling Pathway ◽  
Published Data ◽  
Undifferentiated Cells ◽  
Oncologic Diseases ◽  
Worse Prognosis

Background. The components of the Notch signaling pathway are important in maintaining the balance involved in cell proliferation, apoptosis and differentiation. Therefore, dysfunction of the Notch prevents differentiation, ultimately guiding undifferentiated cells toward malignant transformation. The aim of this article is to present recently published data concerning the role of the Notch signaling pathway components in development and prognosis of oncologic diseases, in occurrence of resistance to cytostatic agents and importance in creating of new cancer treatment approaches. Materials and methods. The Pubmed was the main source of looking for information for this article. Results. Recent investigations show that disorders of the Notch signaling pathway are associated with development of some human haematological and solid cancers. In different tissues and organs this active pathway can act as a tumor suppressor or an oncogene. Accordingly, the increased or decreased expression of its components is defined. Most of published data show that the increased expression of Notch pathway components correlates with a worse prognosis of cancer and a shorter survival. Recently, the Notch pathway has been reported to be involved in drug resistance. The modulation of the Notch signaling pathway could be helpful in treatment of some tumors with abnormal activity of this pathway’s components. Therefore changes in the expression of Notch components could become important predictive factors, helpful in selecting the proper treatment method. Conclusions. The results of recent studies are very important, since the detecting of the prognostic and predictive value of components of the Notch signaling pathway can allow creating new and improving already known methods of cancer diagnostic and treatment.

scholarly journals THE ROLE OF MRNA LEVEL OF THE NOTCH SIGNALING PATHWAY GENES IN INDUCED RAT LIVER FIBROGENESIS

2021 ◽  
Vol 20 (2) ◽  
pp. 25-37
Author(s):  
A.T. Shchastniy ◽  
◽  
E.I. Lebedeva ◽  
A.S. Babenka ◽  
◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Rat Liver ◽  
Mrna Level ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Mrna Levels ◽  
Starting Point ◽  
Liver Fibrogenesis

Objectives. To study the role of mRNA level of the Notch signaling pathway genes in induced rat liver fibrogenesis. Material and methods. Fibrosis followed by the transition to liver cirrhosis in rats of Wistar line was induced with thioacetamide at a dose of 200 mg/kg of animal body weight twice a week for 17 weeks. The rats were randomized into 9 groups of 12 animals each. The mRNA level of the Notch signaling pathway genes was assessed by real-time PCR. The notch1, notch2, yap1 and hes1 genes were used as molecular targets. Microscopic analysis of histological preparations was performed using the OLYMPUS BX51 microscope. The degree of fibrosis was assessed according to the scale of Ishak K.G. Results. The study of the classical transcription factor of the Notch signaling pathway, hes1, revealed its very low and stable activity in all studied samples. The analysis of relative dynamics of the mRNA level of the notch1, notch2, and yap1 genes made it possible to determine marked changes in their levels at the point of transition from the normal state of liver tissues to the development of fibrosis. Conclusions. Within the framework of this study, the hes1 gene is not a target of the Notch pathway and can be used as a reference gene. The noted decrease in the mRNA level of the yap1 gene, probably, inhibits the compensatory-restorative processes in the liver, activates the stellate cells, and promotes the transformation of fibrosis into cirrhosis. In addition, it has been found that the revealed fluctuations in the mRNA levels of the notch1 and yap1 genes in relation to the starting point (there are no changes in the liver tissue) quite accurately describe the period of the onset of the transition of advanced fibrosis to cirrhosis. In this regard, they can be considered as potential markers of the transition of fibrosis to cirrhosis.

scholarly journals The Notch Pathway in Breast Cancer Progression

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Emmanuel N. Kontomanolis ◽  
Sofia Kalagasidou ◽  
Stamatia Pouliliou ◽  
Xanthoula Anthoulaki ◽  
Nikolaos Georgiou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Breast Cancer Progression ◽  
Notch Receptors ◽  
The Impact

Objective. Notch signaling pathway is a vital parameter of the mammalian vascular system. In this review, the authors summarize the current knowledge about the impact of the Notch signaling pathway in breast cancer progression and the therapeutic role of Notch’s inhibition.Methods. The available literature in MEDLINE, PubMed, and Scopus, regarding the role of the Notch pathway in breast cancer progression was searched for related articles from about 1973 to 2017 including terms such as “Notch,” “Breast Cancer,” and “Angiogenesis.”Results. Notch signaling controls the differentiation of breast epithelial cells during normal development. Studies confirm that the Notch pathway has a major participation in breast cancer progression through overexpression and/or abnormal genetic type expression of the notch receptors and ligands that determine angiogenesis. The cross-talk of Notch and estrogens, the effect of Notch in breast cancer stem cells formation, and the dependable Notch overexpression during breast tumorigenesis have been studied enough and undoubtedly linked to breast cancer development. The already applied therapeutic inhibition of Notch for breast cancer can drastically change the course of the disease.Conclusion. Current data prove that Notch pathway has a major participation and multiple roles during breast tumor progression. Inhibition of Notch receptors and ligands provides innovative therapeutic results and could become the therapy of choice in the next few years, even though further research is needed to reach safe conclusions.

scholarly journals Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1264-1273 ◽  
Author(s):  
Melanie G. Cornejo ◽  
Vinciane Mabialah ◽  
Stephen M. Sykes ◽  
Tulasi Khandan ◽  
Cristina Lo Celso ◽  
...  
Keyword(s):  
Stem Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Differentiation ◽  
Notch Signaling Pathway ◽  
Developmental Pathways ◽  
Lineage Specification ◽  
Hematopoietic Stem

Abstract The NOTCH signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. However, the molecular basis for its role at the different steps of stem cell lineage commitment is unclear. We recently identified the NOTCH signaling pathway as a positive regulator of megakaryocyte lineage specification during hematopoiesis, but the developmental pathways that allow hematopoietic stem cell differentiation into the erythro-megakaryocytic lineages remain controversial. Here, we investigated the role of downstream mediators of NOTCH during megakaryopoiesis and report crosstalk between the NOTCH and PI3K/AKT pathways. We demonstrate the inhibitory role of phosphatase with tensin homolog and Forkhead Box class O factors on megakaryopoiesis in vivo. Finally, our data annotate developmental mechanisms in the hematopoietic system that enable a decision to be made either at the hematopoietic stem cell or the committed progenitor level to commit to the megakaryocyte lineage, supporting the existence of 2 distinct developmental pathways.

scholarly journals Epidermoid cyst in a patient with Alagille syndrome: Coincidence or connection?

2020 ◽  
Vol 11 ◽  
pp. 432
Author(s):  
Akhil Surapaneni ◽  
John Kuo ◽  
Min Wang ◽  
Ramsey Ashour
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Epidermoid Cyst ◽  
Alagille Syndrome ◽  
Notch Signaling Pathway ◽  
Syndrome Patient ◽  
Benign Lesions ◽  
Genetic Syndrome ◽  
Epidermoid Cysts

Background: Alagille syndrome is a rare genetic syndrome, which arises due to defects in the Notch signaling pathway, resulting in liver, cardiopulmonary, renal, skeletal, and ophthalmologic problems, among others. Epidermoid cysts are rare congenital benign lesions that develop from ectopic ectodermal cell rests formed during neurulation. Case Description: A 24-year-old Alagille syndrome patient presented with hearing loss and was found to have a sizable posterior fossa mass. He underwent craniotomy for uneventful resection of the lesion, which was found to be an epidermoid cyst. Conclusion: While our case may represent a coincidental occurrence of two pathologies presenting together, given that epidermoid cysts arise from aberrant neurulation, and in light of the crucial role of the Notch signaling pathway both in normal neurogenesis and in the pathogenesis of Alagille syndrome, we hypothesize a possible association between these entities.

Hairy/E(spl)-related(Her) genes are central components of the segmentation oscillator and display redundancy with the Delta/Notch signaling pathway in the formation of anterior segmental boundaries in the zebrafish

Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2929-2946 ◽  
Author(s):  
Andrew C. Oates ◽  
Robert K. Ho
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Central Component ◽  
Mutant Genotype ◽  
Her Family ◽  
Somite Formation ◽  
Anterior Segments ◽  
Her Genes

We have examined the expression of a Hairy/E(spl)-related (Her) gene, her7, in the zebrafish and show that its expression in the PSM cycles similarly to her1 and deltaC. A decrease in her7 function generated by antisense oligonucleotides disrupts somite formation in the posterior trunk and tail, and disrupts the dynamic expression domains of her1 and deltaC, suggesting that her7 plays a role in coordinating the oscillations of neighboring cells in the presomitic mesoderm. This phenotype is reminiscent of zebrafish segmentation mutants with lesions in genes of the Delta/Notch signaling pathway, which also show a disruption of cyclic her7 expression. The interaction of HER genes with the Delta/Notch signaling system was investigated by introducing a loss of her7 function into mutant backgrounds. This leads to segmental defects more anterior than in either condition alone. Combining a decrease of her7 function with reduction of her1 function results in an enhanced phenotype that affects all the anterior segments, indicating that Her functions in the anterior segments are also partially redundant. In these animals, gene expression does not cycle at any time, suggesting that a complete loss of oscillator function had been achieved. Consistent with this, combining a reduction of her7 and her1 function with a Delta/Notch mutant genotype does not worsen the phenotype further. Thus, our results identify members of the Her family of transcription factors that together behave as a central component of the oscillator, and not as an output. This indicates, therefore, that the function of the segmentation oscillator is restricted to the positioning of segmental boundaries. Furthermore, our data suggest that redundancy between Her genes and genes of the Delta/Notch pathway is in part responsible for the robust formation of anterior somites in vertebrates.

scholarly journals The Carcinogenic Role of the Notch Signaling Pathway in the Development of Hepatocellular Carcinoma

2019 ◽  
Vol 10 (6) ◽  
pp. 1570-1579 ◽  
Author(s):  
Qinfeng Huang ◽  
Junhong Li ◽  
Jinghui Zheng ◽  
Ailing Wei
Keyword(s):  
Hepatocellular Carcinoma ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway

The Notch signalling pathway and breast cancer: The importance of balance and cellular self-control.

2019 ◽  
Vol 14 ◽  
Author(s):  
Germán Saucedo-Correa ◽  
Alejandro Bravo-Patiño ◽  
Rosa Elvira Núñez-Anita ◽  
Javier Oviedo-Boyso ◽  
Juan José Valdez-Alarcón ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cross Talk ◽  
Transcriptional Activation ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Self Control ◽  
Design Strategies ◽  
Notch Intracellular Domain ◽  
The Cross

Notch is a cell-signaling pathway that is highly conserved in all metazoans and is responsible for cell differentiation and cross-talk communication with other signaling pathways such as WNT and Hh. In most cancers, the Notch signaling pathway is altered, causing atypical activity of vital processes such as cell cycle, differentiation and apoptosis, leading the cell to a carcinogenic state. Currently, the Notch signaling pathway has taken a special interest to design strategies in order to regulate the activity of this pathway since it is known that in the cancer molecular micro-environment the Notch pathway is over-expressed or presents an aberrant function, which, in consequence, corrupts the cross-talk communication with WNT and Hh pathways. Most of the existing strategies are focused on the systematic and whole inhibition of Notch pathway at the membrane level by the use of γ-secretases inhibitors. There are few strategies that act at the nuclear level inhibiting the activity of the transcriptional activation complex composed by the Notch intracellular domain, the transcriptional factor CSL and the Mastermind co-activator. In this review, by the fact that there are not any strategy focused to revert the over expression effect caused by the Notch pathway constitutive activity, we propose that the efforts to develop new strategies against cancer should be focused to understand the complexity of the cross-talk communication between Notch, WNT and Hh pathways to neutralize the gene aberrant activity characteristic of cancer cells which are responsible for those corrupted cross-talk communication.

scholarly journals Cancer Stem Cells, Quo Vadis? The Notch Signaling Pathway in Tumor Initiation and Progression

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1879 ◽  
Author(s):  
Christian T. Meisel ◽  
Cristina Porcheri ◽  
Thimios A. Mitsiadis
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Adult Life ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Fine Tuning ◽  
Cell Fate Decisions

The Notch signaling pathway regulates cell proliferation, cytodifferentiation and cell fate decisions in both embryonic and adult life. Several aspects of stem cell maintenance are dependent from the functionality and fine tuning of the Notch pathway. In cancer, Notch is specifically involved in preserving self-renewal and amplification of cancer stem cells, supporting the formation, spread and recurrence of the tumor. As the function of Notch signaling is context dependent, we here provide an overview of its activity in a variety of tumors, focusing mostly on its role in the maintenance of the undifferentiated subset of cancer cells. Finally, we analyze the potential of molecules of the Notch pathway as diagnostic and therapeutic tools against the various cancers.

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