scholarly journals RBP-Jκ-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development

2006 ◽  
Vol 26 (13) ◽  
pp. 4769-4774 ◽  
Author(s):  
Céline Souilhol ◽  
Sarah Cormier ◽  
Kenji Tanigaki ◽  
Charles Babinet ◽  
Michel Cohen-Tannoudji
Keyword(s):  
Embryonic Development ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Preimplantation Embryos ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Evolutionarily Conserved

ABSTRACT The Notch signaling pathway is an evolutionarily conserved signaling system which has been shown to be essential in cell fate specification and in numerous aspects of embryonic development in all metazoans thus far studied. We recently demonstrated that several components of the Notch signaling pathway, including the four Notch receptors and their five ligands known in mammals, are expressed in mouse oocytes, in mouse preimplantation embryos, or both. This suggested a possible implication of the Notch pathway in the first cell fate specification of the dividing mouse embryo, which results in the formation of the blastocyst. To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh, a key element of the core Notch signaling pathway, were abrogated. We find that such zygotes give rise to blastocysts which implant and develop normally. Nevertheless, after gastrulation, these embryos die around midgestation, similarly to Rbpsuh-null mutants. This demonstrates that the RBP-Jκ-dependent pathway, otherwise called the canonical Notch pathway, is dispensable for blastocyst morphogenesis and the establishment of the three germ layers, ectoderm, endoderm, and mesoderm. These results are discussed in the light of recent observations which have challenged this conclusion.

NOTCH signaling pathway is required for bovine early embryonic development

2021 ◽  
Author(s):  
Shuang Li ◽  
Yan Shi ◽  
Yanna Dang ◽  
Lei Luo ◽  
Bingjie Hu ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Developmental Competence ◽  
Early Embryonic Development ◽  
Preimplantation Embryos ◽  
Early Embryos ◽  
Genes Encoding

Abstract The NOTCH signaling pathway plays an important role in regulating various biological processes, including lineage specification and apoptosis. Multiple components of the NOTCH pathway have been identified in mammalian preimplantation embryos. However, the precise role of the NOTCH pathway in early embryonic development is poorly understood, especially in large animals. Here, we show that the expression of genes encoding key transcripts of the NOTCH pathway is dynamic throughout early embryonic development. We also confirm the presence of active NOTCH1 and RBPJ. By using pharmacological and RNAi tools, we demonstrate that the NOTCH pathway is required for the proper development of bovine early embryos. This functional consequence could be partly attributed to the major transcriptional mediator-RBPJ, whose deficiency also compromised the embryo quality. Indeed, both NOTCH1 and RBPJ knockdown cause a significant increase of histone H3 serine 10 phosphorylation (pH3S10, a mitosis marker) positive blastomeres, suggesting a cell cycle arrest at mitosis. Importantly, RNA-seq analyses reveal that either NOTCH1 or RBPJ depletion triggers a reduction in H1FOO that encodes the oocyte-specific linker histone H1 variant. Interestingly, depleting H1FOO results in detrimental effects on the developmental competence of early embryos, similar with NOTCH1 inhibition. Overall, our results reveal a crucial role for NOTCH pathway in regulating bovine preimplantation development, likely by controlling cell proliferation and maintaining H1FOO expression.

scholarly journals The developmental origins of Notch-driven intrahepatic bile duct disorders

2021 ◽  
Vol 14 (9) ◽  
Author(s):  
Anabel Martinez Lyons ◽  
Luke Boulter
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Cellular Proliferation ◽  
Intrahepatic Bile Duct ◽  
Cell Communication ◽  
Notch Signaling Pathway ◽  
Cell Fate Specification ◽  
Evolutionarily Conserved ◽  
Embryonic Life

ABSTRACT The Notch signaling pathway is an evolutionarily conserved mechanism of cell–cell communication that mediates cellular proliferation, cell fate specification, and maintenance of stem and progenitor cell populations. In the vertebrate liver, an absence of Notch signaling results in failure to form bile ducts, a complex tubular network that radiates throughout the liver, which, in healthy individuals, transports bile from the liver into the bowel. Loss of a functional biliary network through congenital malformations during development results in cholestasis and necessitates liver transplantation. Here, we examine to what extent Notch signaling is necessary throughout embryonic life to initiate the proliferation and specification of biliary cells and concentrate on the animal and human models that have been used to define how perturbations in this signaling pathway result in developmental liver disorders.

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.

Notch Signaling Pathway: Find New Channel during Liver Repair and Regeneration

2021 ◽  
Vol 28 ◽  
Author(s):  
Amir Valizadeh ◽  
Ali Sayadmanesh ◽  
Zatollah Asemi ◽  
Forough Alemi ◽  
Ata Mahmoodpoor ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
The Body ◽  
Liver Disorders ◽  
Liver Repair ◽  
Underlying Mechanisms

: The liver is one of the significant regenerative organs in the body. Nevertheless, underlying molecular mechanisms regulating liver repair and regeneration following resection or damage remain largely unknown. The Notch signaling pathway is a profoundly evolutionarily well‐conserved cell signaling system that plays mostly in multicellular organisms' development. Malfunctions in this pathway lead to the progression of several liver disorders, including hepatoblastoma (HB), cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), and so on. Notch pathway plays a fundamental role in cell fate during the embryonic stage's progression to the adult stage in liver tissue. Modulation of Notch signaling may be used in the vast array of patients who succumb to cirrhosis owing to chronic hepatitis by virus infection. This review describes the underlying mechanisms of the Notch signaling pathway in liver development and regeneration briefly and discusses how this pathway leads to better liver disorders in the clinic.

scholarly journals Notch Signaling in T-Cell Development and T-ALL

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoyu Li ◽  
Harald von Boehmer
Keyword(s):  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Notch Signaling Pathway ◽  
Lineage Specification ◽  
Evolutionarily Conserved ◽  
Multiple Levels ◽  
Multicellular Organisms ◽  
T Cell Maturation

The Notch signaling pathway is an evolutionarily conserved cell signaling system present in most multicellular organisms, as it controls cell fate specification by regulating cell proliferation, differentiation, apoptosis, and survival. Regulation of the Notch signaling pathway can be achieved at multiple levels. Notch proteins are involved in lineage fate decisions in a variety of tissues in various species. Notch is essential for T lineage cell differentiation including T versus B and αβ versus γδ lineage specification. In this paper, we discuss Notch signaling in normal T-cell maturation and differentiation as well as in T-cell acute lymphoblastic lymphoma/leukemia.

scholarly journals EXPRESIÓN DE LOS GENES Serrate1 Y Notch1 DURANTE EL DESARROLLO DEL TERCIO MEDIO FACIAL DEL EMBRIÓN DE POLLO

2015 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel Mauricio Meza Lasso ◽  
Cindy Johana Peña Barrera ◽  
Francy Yomara Bayona Rodriguez ◽  
Belfran Alcides Carbonell Medina ◽  
Clementina Infante
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Expression Patterns ◽  
Notch Pathway ◽  
Cell Communication ◽  
Gallus Gallus ◽  
Notch Signaling Pathway ◽  
Cellular Processes

<p class="p1"><strong>RESUMEN</strong></p><p class="p2">La vía de señalización Notch se caracteriza por mediar la comunicación célula-célula, regulando diferentes procesos celulares como proliferación, apoptosis y definición del destino celular. Esta vía ha sido implicada en el desarrollo de estructuras craneofaciales como paladar, diente y bóveda craneal. El objetivo de esta investigación fue identificar los patrones de expresión de los genes componentes de la vía Notch, Serrate1 y Notch1, durante el desarrollo del tercio medio facial. Se utilizaron embriones de pollo (Gallus gallus) seleccionados de acuerdo a los criterios de Hamilton y Hamburger y sobre los cuales se realizó hibridación in situ con ribosondas marcadas con Digoxigenina (DIG), para luego ser detectadas con anticuerpos Anti-Dig. Los resultados mostraron expresión de los genes evaluados, en las prominencias maxilares (pmx) y frontonasal (pfn) durante el desarrollo del tercio medio facial. Estos resultados sugieren una probable participación de la vía Notch a través de estos genes, en los diferentes procesos celulares que determinan la morfogénesis y el desarrollo del tercio medio facial.</p><p class="p2"><strong>ABSTRACT</strong></p><p class="p2">The Notch signaling pathway is characterized by mediate cell-cell communication, regulating different cellular processes as proliferation, apoptosis and cell fate definition. This pathway has been implicated in craniofacial structures development as palate, teeth and cranial vault. The objective of this research was to identify the genes expression patterns of some Notch signaling pathway components, Serrate1 and Notch1, during the midface development. It was used chicken embryos (Gallus gallus) selected according to Hamilton and Hamburger criteria. We performed in situ hybridization with Digoxigenin (DIG)-labeled riboprobes and detected with the antibody Anti-Dig. The results showed the expression of the evaluated genes in the maxillary (pmx) and frontonasal (pfn) prominences during the midface development. These results suggest a probable involvement of the Notch pathway through these genes in different cellular processes that determine midface morphogenesis and development.</p><p class="p2"> </p>

scholarly journals Notch Signaling during Oogenesis in Drosophila melanogaster

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jingxia Xu ◽  
Thomas Gridley
Keyword(s):  
Drosophila Melanogaster ◽  
Notch Signaling ◽  
Cell Fate ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Intercellular Signaling ◽  
Signaling Mechanism ◽  
Stem Cell Maintenance ◽  
Evolutionarily Conserved ◽  
Biochemical Mechanisms

The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism that is required for embryonic development, cell fate specification, and stem cell maintenance. Discovered and studied initially in Drosophila melanogaster, the Notch pathway is conserved and functionally active throughout the animal kingdom. In this paper, we summarize the biochemical mechanisms of Notch signaling and describe its role in regulating one particular developmental pathway, oogenesis in Drosophila.

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.

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.

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