scholarly journals Estrogen and EGFR Pathways Regulate Notch Signaling in Opposing Directions for Multi-Ciliogenesis in the Fallopian Tube

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 933 ◽  
Author(s):  
Zhu ◽  
Iwano ◽  
Takeda
Keyword(s):  
Estrogen Receptor ◽  
Notch Signaling ◽  
Cell Fate ◽  
Fallopian Tube ◽  
Culture System ◽  
Notch Signaling Pathway ◽  
Estrogen Signaling ◽  
Ciliated Cells ◽  
Epithelial Homeostasis ◽  
Epidermal Growth

The lumen of the fallopian tube (FT) is lined with columnar epithelium composed of secretory and ciliated cells, both of which are important for reproduction. However, the molecular mechanism regulating cell fate remains controversial. In this study, we established a primary culture system using porcine fallopian tube epithelial cells (FTECs) to study the differentiation mechanism. We found that estrogen promoted the differentiation of multi-ciliated cells (MCCs) through estrogen receptor β, following the reduction of DLL1, a ligand of Notch. Meanwhile, epidermal growth factor (EGF), a regulator of epithelial homeostasis and differentiation, suppressed ciliogenesis by the activation of Notch signaling. However, the estrogen pathway did not affect the activation of the EGF pathway. Taken together, the differentiation of MMCs in FT depends on the balance of EGF and estrogen signaling, either of which inhibits or stimulates the Notch signaling pathway respectively.

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 Natural Herbal Estrogen-Mimetics (Phytoestrogens) Promote the Differentiation of Fallopian Tube Epithelium into Multi-Ciliated Cells via Estrogen Receptor Beta

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 722
Author(s):  
Maobi Zhu ◽  
Sen Takeda ◽  
Tomohiko Iwano
Keyword(s):  
Estrogen Receptor ◽  
Cell Differentiation ◽  
Epithelial Cells ◽  
Fallopian Tube ◽  
Ciliated Cell ◽  
Estrogen Receptor Beta ◽  
Notch Pathway ◽  
Secretory Cells ◽  
Ciliated Cells ◽  
Receptor Beta

Phytoestrogens are herbal polyphenolic compounds that exert various estrogen-like effects in animals and can be taken in easily from a foodstuff in daily life. The fallopian tube lumen, where transportation of the oocyte occurs, is lined with secretory cells and multi-ciliated epithelial cells. Recently, we showed that estrogen induces multi-ciliogenesis in the porcine fallopian tube epithelial cells (FTECs) through the activation of the estrogen receptor beta (ERβ) pathway and simultaneous inhibition of the Notch pathway. Thus, ingested phytoestrogens may induce FTEC ciliogenesis and thereby affect the fecundity. To address this issue, we added isoflavones (genistein, daidzein, or glycitin) and coumestan (coumestrol) to primary culture FTECs under air–liquid interface conditions and assessed the effects of each compound. All phytoestrogens except glycitin induced multi-ciliated cell differentiation, which followed Notch signal downregulation. On the contrary, the differentiation of secretory cells decreased slightly. Furthermore, genistein and daidzein had a slight effect on the proportion of proliferating cells exhibited by Ki67 expression. Ciliated-cell differentiation is inhibited by the ERβ antagonist, PHTPP. Thus, this study suggests that phytoestrogens can improve the fallopian tube epithelial sheet homeostasis by facilitating the genesis of multi-ciliated cells and this effect depends on the ERβ-mediated pathway.

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.

scholarly journals Delta-1 Activation of Notch-1 Signaling Results inHES-1 Transactivation

1998 ◽  
Vol 18 (12) ◽  
pp. 7423-7431 ◽  
Author(s):  
Sophie Jarriault ◽  
Odile Le Bail ◽  
Estelle Hirsinger ◽  
Olivier Pourquié ◽  
Frédérique Logeat ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Notch Signaling ◽  
Cell Fate ◽  
Notch Signaling Pathway ◽  
Notch Receptor ◽  
Cell Fate Determination ◽  
Notch 1 ◽  
Promoter Construct ◽  
Enhancer Of Split

ABSTRACT The Notch receptor is involved in many cell fate determination events in vertebrates and invertebrates. It has been shown inDrosophila melanogaster that Delta-dependent Notch signaling activates the transcription factor Suppressor of Hairless, leading to an increased expression of the Enhancer of Splitgenes. Genetic evidence has also implicated the kuzbaniangene, which encodes a disintegrin metalloprotease, in the Notch signaling pathway. By using a two-cell coculture assay, we show here that vertebrate Dl-1 activates the Notch-1 cascade. Consistent with previous data obtained with active forms of Notch-1 aHES-1-derived promoter construct is transactivated in cells expressing Notch-1 in response to Dl-1 stimulation. Impairing the proteolytic maturation of the full-length receptor leads to a decrease in HES-1 transactivation, further supporting the hypothesis that only mature processed Notch is expressed at the cell surface and activated by its ligand. Furthermore, we observed that Dl-1-inducedHES-1 transactivation was dependent both on Kuzbanian and RBP-J activities, consistent with the involvement of these two proteins in Notch signaling in Drosophila. We also observed that exposure of Notch-1-expressing cells to Dl-1 results in an increased level of endogenous HES-1 mRNA. Finally, coculture of Dl-1-expressing cells with myogenic C2 cells suppresses differentiation of C2 cells into myotubes, as previously demonstrated for Jagged-1 and Jagged-2, and also leads to an increased level of endogenousHES-1 mRNA. Thus, Dl-1 behaves as a functional ligand for Notch-1 and has the same ability to suppress cell differentiation as the Jagged proteins do.

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.

scholarly journals Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway

2016 ◽  
Vol 129 (13) ◽  
pp. e1.2-e1.2
Author(s):  
Laura Grisanti ◽  
Ekaterina Revenkova ◽  
Ronald E. Gordon ◽  
Carlo Iomini
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Primary Cilia ◽  
Notch Signaling Pathway ◽  
Corneal Epithelial ◽  
Epithelial Homeostasis

scholarly journals An updated evolutionary study of the Notch family reveals a new ancient origin and novel invariable motifs as potential pharmacological targets

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10334
Author(s):  
Dimitrios Vlachakis ◽  
Louis Papageorgiou ◽  
Ariadne Papadaki ◽  
Maria Georga ◽  
Sofia Kossida ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Notch Signaling Pathway ◽  
Evolutionary Analysis ◽  
Cell Fate Decisions ◽  
Pharmacological Targets ◽  
Organ Systems

Notch family proteins play a key role in a variety of developmental processes by controlling cell fate decisions and operating in a great number of biological processes in several organ systems, such as hematopoiesis, somatogenesis, vasculogenesis, neurogenesis and homeostasis. The Notch signaling pathway is crucial for the majority of developmental programs and regulates multiple pathogenic processes. Notch family receptors’ activation has been largely related to its multiple effects in sustaining oncogenesis. The Notch signaling pathway constitutes an ancient and conserved mechanism for cell to cell communication. Much of what is known about Notch family proteins function comes from studies done in Caenorhabditis Elegans and Drosophila Melanogaster. Although, human Notch homologs had also been identified, the molecular mechanisms which modulate the Notch signaling pathway remained substantially unknown. In this study, an updated evolutionary analysis of the Notch family members among 603 different organisms of all kingdoms, from bacteria to humans, was performed in order to discover key regions that have been conserved throughout evolution and play a major role in the Notch signaling pathway. The major goal of this study is the presentation of a novel updated phylogenetic tree for the Notch family as a reliable phylogeny “map”, in order to correlate information of the closely related members and identify new possible pharmacological targets that can be used in pathogenic cases, including cancer.

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 Mechanisms in Endocrinology: Notch signaling in skeletal health and disease

2013 ◽  
Vol 168 (6) ◽  
pp. R95-R103 ◽  
Author(s):  
Stefano Zanotti ◽  
Ernesto Canalis
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Target Genes ◽  
Skeletal Development ◽  
Alagille Syndrome ◽  
Notch Signaling Pathway ◽  
Loss Of Function ◽  
Skeletal Health ◽  
Notch Ligand ◽  
Ligand Interactions

Notch receptors are single-pass transmembrane proteins that determine cell fate. Upon Notch ligand interactions, proteolytic cleavages release the Notch intracellular domain, which translocates to the nucleus to regulate the transcription of target genes, including Hairy enhancer of split (Hes) and Hes related to YRPW motif (Hey). Notch is critical for skeletal development and activity of skeletal cells, and dysregulation of Notch signaling is associated with human diseases affecting the skeleton. Inherited or sporadic mutations in components of the Notch signaling pathway are associated with spondylocostal dysostosis, spondylothoracic dysostosis and recessive brachydactyly, diseases characterized by skeletal patterning defects. Inactivating mutations of the Notch ligandJAG1or ofNOTCH2are associated with Alagille syndrome, and activating mutations inNOTCH2are associated with Hajdu–Cheney syndrome (HCS). Individuals affected by HCS exhibit osteolysis in distal phalanges and osteoporosis. NOTCH is activated in selected tumors, such as osteosarcoma, and in breast cancer cells that form osteolytic bone metastases. In conclusion, Notch regulates skeletal development and bone remodeling, and gain- or loss-of-function mutations of Notch signaling result in important skeletal diseases.

Epidermal growth factor promotes proliferation of dermal papilla cells via Notch signaling pathway

Biochimie ◽  
2016 ◽  
Vol 127 ◽  
pp. 10-18 ◽  
Author(s):  
Haihua Zhang ◽  
Weixiao Nan ◽  
Shiyong Wang ◽  
Tietao Zhang ◽  
Huazhe Si ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Dermal Papilla ◽  
Notch Signaling Pathway ◽  
Dermal Papilla Cells ◽  
Epidermal Growth
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