The Xenopus homolog of Drosophila Suppressor of Hairless mediates Notch signaling during primary neurogenesis

Development ◽  
1997 ◽  
Vol 124 (3) ◽  
pp. 693-702 ◽  
Author(s):  
D.A. Wettstein ◽  
D.L. Turner ◽  
C. Kintner
Keyword(s):  
Dna Binding ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Interaction ◽  
Notch Signaling Pathway ◽  
Notch 1 ◽  
Xenopus Embryos ◽  
Suppressor Of Hairless ◽  
Primary Neurogenesis ◽  
Enhancer Of Split

The X-Notch-1 receptor, and its putative ligand, X-Delta-1, are thought to mediate an inhibitory cell-cell interaction, called lateral inhibition, that limits the number of primary neurons that form in Xenopus embryos. The expression of Xenopus ESR-1, a gene related to Drosophila Enhancer of split, appears to be induced by Notch signaling during this process. To determine how the activation of X-Notch-1 induces ESR-1 expression and regulates primary neurogenesis, we isolated the Xenopus homolog of Suppressor of Hairless (X-Su(H)), a component of the Notch signaling pathway in Drosophila. Using animal cap assays, we show that X-Su(H) induces ESR-1 expression, perhaps directly, when modified by the addition of ankyrin repeats. Using a DNA binding mutant of X-Su(H), we show that X-Su(H) activity is required for induction of ESR-1. Finally, expression of the DNA binding mutant in embryos leads to a neurogenic phenotype as well as increased expression of both X-Delta-1 and XNGNR1, a proneural gene expressed during primary neurogenesis. These results suggest that activation of X-Su(H) is a key step in the Notch signaling pathway during primary neurogenesis in Xenopus embryos.

scholarly journals Synergy between suppressor of Hairless and Notch in regulation of Enhancer of split m gamma and m delta expression.

1997 ◽  
Vol 17 (9) ◽  
pp. 5620-5628 ◽  
Author(s):  
D S Eastman ◽  
R Slee ◽  
E Skoufos ◽  
L Bangalore ◽  
S Bray ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Transcriptional Activation ◽  
Cultured Cells ◽  
Notch Signaling Pathway ◽  
Cell Fate Decisions ◽  
Suppressor Of Hairless ◽  
Enhancer Of Split

The Notch signaling pathway is known to regulate cell fate decisions in a variety of organisms from worms to humans. Although several components of the pathway have been characterized, the actual mechanism and molecular results of signaling remain elusive. We have examined the role of the Notch signaling pathway in the transcriptional regulation of two Drosophila Enhancer of split [E(spl)] genes, whose gene products have been shown to be downstream players in the pathway. Using a reporter assay system in Drosophila tissue culture cells, we have observed a significant induction of E(spl) m gamma and m delta expression after cotransfection with activated Notch. Characterization of the 5' regulatory regions of these two genes led to the identification of a number of target sites for the Suppressor of Hairless [Su(H)] protein, a transcription factor activated by Notch signaling. We show that Notch-inducible expression of E(spl) m gamma and m delta both in cultured cells and in vivo is dependent on functional Su(H). Although overexpression of Su(H) augments the level of induction of the reporter genes by activated Notch, Su(H) alone is insufficient to produce high levels of transcriptional activation. Despite the synergy observed between activated Notch and Su(H), the former affects neither the nuclear localization nor the DNA binding activity of the latter.

Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway.

2020 ◽  
Vol 20 ◽  
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Mohd Saeed ◽  
Irfan Ahmad ◽  
Irfan A. Ansari
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Mtt Assay ◽  
Annexin V ◽  
Notch Signaling Pathway ◽  
Phase Cell ◽  
Ros Generation ◽  
Notch 1

Background: Recently Notch signaling pathway has gained attention as a potential therapeutic target for chemotherapeutic intervention. However, the efficacy of previously known Notch inhibitors in colon cancer is still unclear. The purpose of this study was to investigate the effect of andrographolide on aberrantly activated Notch signaling in SW-480 cells in vitro. Methods: The cytostatic potential of andrographolide on SW-480 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, morphology assessment and colony formation assay. The apoptotic activity was evaluated by FITC Annexin V assay, 4′,6-diamidino-2-phenylindole (DAPI), Hoechst, Rhodamine 123 and Mito Tracker CMXRos staining. Scratch assay for migratory potential assessment. 7’-Dichlorodihydrofluorescein Diacetate (DCFH-DA) staining was used to evaluate the Reactive Oxygen Species (ROS) generation. Relative mRNA expression of Bax, Bcl2, NOTCH 1 and JAGGED 1 was estimated by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Cell cycle phase distribution was evaluated Annexin V-FITC/PI staining. Results: MTT assay demonstrated dose and time dependent cytoxicity of andrographolide on SW-480 cells. It also inhibited the migratory and colony forming potential of SW-480 cells. Furthermore, andrographolide also showed disruption of mitochondrial membrane potential and induced apoptosis through nuclear condensation. Flow cytometric evaluation showed andrographolide enhanced early and late apoptotic cells and induced upregulation of proapoptotic (Bax and Bad) and downregulation of antiapoptotic Bcl2 in treated SW-480 cells. Andrographolide augmented intracellular ROS generation and induced G0/G1 phase cell cycle arrest in colon cancer SW480 cells. Furthermore, andrographolide repressed the Notch signaling by decreasing the expression of NOTCH 1 and JAGGED 1. Conclusion: Our findings suggested that andrographolide constraint the growth of SW-480 cells through the inhibition of Notch signaling pathway.

scholarly journals Bufei Qingyu Granules Inhibit the Development of Systemic Sclerosis via Notch-1/Jagged-2 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Minhui Su ◽  
Fang Tian ◽  
Bingchen Ouyang ◽  
Xiaoyu Wu ◽  
Feng Guo ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Smooth Muscle Actin ◽  
Notch Signaling Pathway ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Notch 1 ◽  
Bioinformatics Analyses

Systemic sclerosis (SSc) is a rare chronic autoimmune disorder, mainly characterized by skin sclerosis. In this study, Bufei Qingyu Granules (BQG), a Chinese herbal formula, was used to treat SSc. To better understand the effects and molecular mechanisms of BQG, we successfully established a Bleomycin- (BLM-) induced SSc mouse model, and the mice were treated by BQG. Meanwhile, transcriptomic and bioinformatics analyses were conducted on those samples. As a result, we visually showed that BQG ameliorated the overall health of mice, including body weight, spleen, and thymus index. Thus, it also significantly alleviated inflammation presented by Chemokine (C-X-C motif) ligand 2 (Cxcl2), vasculopathy characterized by α-smooth muscle actin (α-SMA), and fibrotic changes elaborated by not only pathological images, but also the hydroxyproline (HYP) content. After testing by transcriptomic analysis, Cxcl2, Synaptosomal-associated protein 25 (Snap25), and Eukaryotic translation initiation factor 3, and subunit J2 (Eif3j2) which were differentially expressed genes, were verified, so that the data were credible. We further found that BQG could regulate Notch signaling pathway by significantly decreasing both mRNA and protein expression levels of Notch-1 and Jagged-2. Hence, this study demonstrated that BQG could ameliorate the sclerotic skin in mice model involved in inflammation, vascular changes, and fibrosis effects, which was partly mediated by Notch signaling pathway.

Role of Hairless and Suppressor of Hairless in the Notch signaling pathway in Drosophila

1995 ◽  
Vol 84 (1-2) ◽  
pp. 89-89
Author(s):  
M. Lecourtois ◽  
C. Brou ◽  
F. Logeat ◽  
A. Israel ◽  
F. Schweisguth
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Suppressor Of Hairless

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 The Notch Pathway Intermediate HES-1 Silences CD4 Gene Expression

1998 ◽  
Vol 18 (12) ◽  
pp. 7166-7175 ◽  
Author(s):  
Han K. Kim ◽  
Gerald Siu
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Transcriptional Control ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Thymic Development ◽  
Enhancer Function ◽  
Enhancer Of Split

ABSTRACT We have previously identified a transcriptional silencer that is critical for proper expression of the CD4 gene during T-cell development. Here we report that the Hairy/Enhancer of Split homologue HES-1, a transcription factor in the lin12/Notch signaling pathway, binds to an important functional site in the CD4 silencer. Overexpression of HES-1 leads to the silencer site-dependent repression of CD4 promoter and enhancer function as well as the downregulation of endogenous CD4 expression in CD4+ CD8−TH cells. Interestingly, overexpression of an activated form of Notch1 (NotchIC) leads to the repression of CD4 promoter and enhancer function both in the presence and absence of the silencer. NotchIC-mediated CD4 silencer function is not affected by the deletion of the HES-1-binding site, indicating that multiple factors binding to CD4 transcriptional control elements are responsive to signaling from this pathway, including other silencer-binding factors. Taken together, these data are consistent with the hypothesis that the lin12/Notch signaling pathway is important in thymic development and provide a molecular mechanism via the control of CD4 gene expression in which the lin12/Notch pathway affects T-cell developmental fate.

scholarly journals Xenopus embryos show a compensatory response following perturbation of the Notch signaling pathway

2020 ◽  
Vol 460 (2) ◽  
pp. 99-107
Author(s):  
Grace E. Solini ◽  
Mark E. Pownall ◽  
Molly J. Hillenbrand ◽  
Claire E. Tocheny ◽  
Sudip Paudel ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Compensatory Response ◽  
Xenopus Embryos

scholarly journals Έκφραση του σηματοδοτικού μονοπατιού Notch σε πλακούντες εγκύων με προεκλαμψία

2015 ◽  
Author(s):  
Περσεφόνη Φραγκιαδάκη
Keyword(s):  
Western Blot ◽  
Notch Signaling ◽  
Real Time ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Target Genes ◽  
Notch Signaling Pathway ◽  
Quantitative Real Time Pcr ◽  
Notch 1 ◽  
Qrt Pcr

Η προεκλαμψία αποτελεί μια από τις κυριότερες αιτίες μητρικής και εμβρυικής/νεογνικής νοσηρότητας και θνητότητας και επιπλέκει το 3-5% των κυήσεων. Προηγούμενες μελέτες έδειξαν ότι μέλη του σηματοδοτικού μονοπατιού Notch (Notch signaling pathway) εκφράζονται στον πλακούντα και παίζουν σημαντικό ρόλο στην ομαλή ανάπτυξη του ενεργοποιώντας μεταγραφικούς παράγοντες οι οποίοι αλλάζουν την έκφραση γονιδίων στόχων. Διαταραχές στη λειτουργία του μονοπατίου Notch σχετίζονται με παθολογική πλακουντοποίηση. Σκοπός της μελέτης αυτής είναι να εξετάσει την έκφραση των υποδοχέων (receptors) NOTCH1,-2,-3,-4, των συνδετών (ligands) DLL1,-3,-4, JAG1,-2 και των γονιδίων στόχων (target genes) HEY1,-2 σε πλακούντες κυήσεων με προεκλαμψία. Εξετάστηκαν δείγματα πλακουντιακού ιστού από 20 προεκλαμπτικές και από 20 φυσιολογικές κυήσεις. Τα επίπεδα mRNA των υπό εξέταση μορίων μετρήθηκαν με ποσοτική (quantitative) Real-Time PCR (qRT-PCR) ενώ η πρωτεϊνική έκφραση της ενδοκυττάριας περιοχής (intracellular domain) των NOTCH2 (NICD2) και NOTCH3 (NICD3) εκτιμήθηκαν με Western Blot (WB). Τα αποτελέσματα μας έδειξαν ότι οι υποδοχείς Notch-1 και Notch-4 αλλά και ο συνδέτης Dll-1 δεν εκφράζονται στους πλακούντες γυναικών με προεκλαμψία ή με φυσιολογική εγκυμοσύνη. Ωστόσο, τα επίπεδα έκφρασης mRNA των NOTCH2, NOTCH3, DLL3, DLL4, JAG1, JAG2, HEY1 and HEY2 ήταν μειωμένα στα παθολογικά δείγματα σε σχέση με τα φυσιολογικά (p<0.01). Η ανάλυση με WB επιβεβαίωσε ότι τα επίπεδα πρωτεϊνικής έκφρασης των NICD2 και NICD3 ήταν επίσης ελαττωμένα στα δείγματα της προεκλαμψίας (p=0.014 και p<0.001, αντίστοιχα). Περαιτέρω στατιστική ανάλυση έδειξε α) μη έκφραση σε γονιδιακό επίπεδο του υποδοχέα NOTCH3 στις εγκύους εκείνες που κάπνιζαν και στη διάρκεια της εγκυμοσύνης σε σχέση με εκείνες που το έκοψαν (p=0.029) και β) στις περιπτώσεις με προεκλαμψία και βάρος νεογνού μικρότερο από την 5η εκατοστιαία θέση παρατηρήσαμε υψηλότερα επίπεδα πρωτεΐνης του NICD-3 (p=0.028) και υψηλότερα επίπεδα mRNA του Dll-3 (p=0.041). Τα αποτελέσματα της μελέτης μας δείχνουν ότι το σηματοδοτικό μονοπάτι Notch αποτελεί σημαντικό μέρος της παθογένειας αυτής της επιπλοκής της εγκυμοσύνης. Περαιτέρω μελέτες απαιτούνται με σκοπό να διερευνηθεί βαθύτερα και να καθοριστεί ο ρόλος των εξετασθέντων μορίων στην προεκλαμψία και να μελετηθεί η δυνητική τους χρήση στην πρόβλεψη και τη διαγνωστική και θεραπευτική προσέγγιση της νόσου.

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