Notch Signaling-Induced Oscillatory Gene Expression May Drive Neurogenesis in the Developing Retina

Context: Notch genes encode receptors for a signaling pathway that regulates cell growth and differentiation in various contexts, but the role of Notch signaling in thyroid follicular cells has never been fully published. Objective: The objective of the study was to characterize the expression of Notch pathway components in thyroid follicular cells and Notch signaling activities in normal and transformed thyrocytes. Design/Setting and Patients: Expression of Notch pathway components and key markers of thyrocyte differentiation was analyzed in murine and human thyroid tissues (normal and tumoral) by quantitative RT-PCR and immunohistochemistry. The effects of Notch overexpression in human thyroid cancer cells and FTRL-5 cells were explored with analysis of gene expression, proliferation assays, and experiments involving transfection of a luciferase reporter construct containing human NIS promoter regions. Results: Notch receptors are expressed during the development of murine thyrocytes, and their expression levels parallel those of thyroid differentiation markers. Notch signaling characterized also normal adult thyrocytes and is regulated by TSH. Notch pathway components are variably expressed in human normal thyroid tissue and thyroid tumors, but expression levels are clearly reduced in undifferentiated tumors. Overexpression of Notch-1 in thyroid cancer cells restores differentiation, reduces cell growth rates, and stimulates NIS expression via a direct action on the NIS promoter. Conclusion: Notch signaling is involved in the determination of thyroid cell fate and is a direct regulator of thyroid-specific gene expression. Its deregulation may contribute to the loss of differentiation associated with thyroid tumorigenesis.

Download Full-text

3P278 Role of intronic delay in oscillatory gene expression(24. Mathematical biology,Poster,The 52nd Annual Meeting of the Biophysical Society of Japan(BSJ2014))

Seibutsu Butsuri ◽

10.2142/biophys.54.s295_2 ◽

2014 ◽

Vol 54 (supplement1-2) ◽

pp. S295

Author(s):

Bhaswati Bhattacharyya ◽

Ziya Kalay

Keyword(s):

Gene Expression ◽

Mathematical Biology ◽

Annual Meeting ◽

Biophysical Society ◽

Oscillatory Gene Expression

Download Full-text

Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis

Development ◽

10.1242/dev.127.17.3865 ◽

2000 ◽

Vol 127 (17) ◽

pp. 3865-3876

Author(s):

M.S. Rones ◽

K.A. McLaughlin ◽

M. Raffin ◽

M. Mercola

Keyword(s):

Gene Expression ◽

Notch Signaling ◽

Cell Fate ◽

Notch Pathway ◽

Cell Types ◽

Myocardial Cell ◽

Dominant Negative ◽

Cell Fates ◽

Cell Fate Decisions ◽

Heart Field

Notch signaling mediates numerous developmental cell fate decisions in organisms ranging from flies to humans, resulting in the generation of multiple cell types from equipotential precursors. In this paper, we present evidence that activation of Notch by its ligand Serrate apportions myogenic and non-myogenic cell fates within the early Xenopus heart field. The crescent-shaped field of heart mesoderm is specified initially as cardiomyogenic. While the ventral region of the field forms the myocardial tube, the dorsolateral portions lose myogenic potency and form the dorsal mesocardium and pericardial roof (Raffin, M., Leong, L. M., Rones, M. S., Sparrow, D., Mohun, T. and Mercola, M. (2000) Dev. Biol., 218, 326–340). The local interactions that establish or maintain the distinct myocardial and non-myocardial domains have never been described. Here we show that Xenopus Notch1 (Xotch) and Serrate1 are expressed in overlapping patterns in the early heart field. Conditional activation or inhibition of the Notch pathway with inducible dominant negative or active forms of the RBP-J/Suppressor of Hairless [Su(H)] transcription factor indicated that activation of Notch feeds back on Serrate1 gene expression to localize transcripts more dorsolaterally than those of Notch1, with overlap in the region of the developing mesocardium. Moreover, Notch pathway activation decreased myocardial gene expression and increased expression of a marker of the mesocardium and pericardial roof, whereas inhibition of Notch signaling had the opposite effect. Activation or inhibition of Notch also regulated contribution of individual cells to the myocardium. Importantly, expression of Nkx2. 5 and Gata4 remained largely unaffected, indicating that Notch signaling functions downstream of heart field specification. We conclude that Notch signaling through Su(H) suppresses cardiomyogenesis and that this activity is essential for the correct specification of myocardial and non-myocardial cell fates.

Download Full-text

Oscillatory gene expression and somitogenesis

Wiley Interdisciplinary Reviews Developmental Biology ◽

10.1002/wdev.46 ◽

2012 ◽

Vol 1 (5) ◽

pp. 629-641 ◽

Cited By ~ 44

Author(s):

Ryoichiro Kageyama ◽

Yasutaka Niwa ◽

Akihiro Isomura ◽

Aitor González ◽

Yukiko Harima

Keyword(s):

Gene Expression ◽

Oscillatory Gene Expression

Download Full-text

Foxi1 inactivation rescues loss of principal cell fate selection in Hes1-deficient kidneys but does not ensure maintenance of principal cell gene expression

10.1101/826610 ◽

2019 ◽

Author(s):

Malini Mukherjee ◽

Jennifer DeRiso ◽

Madhusudhana Janga ◽

Eric Fogarty ◽

Kameswaran Surendran

Keyword(s):

Gene Expression ◽

Notch Signaling ◽

Cell Fate ◽

Collecting Duct ◽

Cell Types ◽

Principal Cell ◽

Intercalated Cell ◽

Collecting Ducts ◽

Cell Gene Expression ◽

Cell Gene

AbstractThe distal nephron and collecting duct segments of the mammalian kidney consist of intercalated cell types intermingled among principal cell types. Notch signaling ensures that a sufficient number of cells select a principal instead of an intercalated cell fate. However, the precise mechanisms by which Notch signaling patterns the distal nephron and collecting duct cell fates is unknown. Here we observed that Hes1, a direct target of Notch signaling pathway, is required within the mouse developing collecting ducts for repression of Foxi1 expression, an essential intercalated cell specific transcription factor. Interestingly, inactivation of Foxi1 in Hes1-deficient collecting ducts rescues the deficiency in principal cell fate selection, overall urine concentrating deficiency, and reduces the occurrence of hydronephrosis. However, Foxi1 inactivation does not rescue the reduction in expression of all principal cell genes in the Hes1-deficient kidney collecting duct cells that select the principal cell fate. Additionally, suppression of Notch/Hes1 signaling in mature principal cells reduces principal cell gene expression without activating Foxi1. We conclude that Hes1 is a Notch signaling target that is essential for normal patterning of the collecting ducts with intermingled cell types by repressing Foxi1, and for maintenance of principal cell gene expression independent of repressing Foxi1.

Download Full-text

Retinal Genomic Fabrics Remodeling after Optic Nerve Injury

10.20944/preprints202004.0016.v2 ◽

2021 ◽

Author(s):

Pedro Henrique Victorino ◽

Camila Marra ◽

Dumitru Andrei Iacobas ◽

Sanda Iacobas ◽

David C Spray ◽

...

Keyword(s):

Gene Expression ◽

Optic Nerve ◽

Notch Signaling ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Notch Signaling Pathway ◽

Complement Cascade ◽

Gene Expressions ◽

Nerve Crush ◽

Individual Gene

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

Download Full-text

Developmental compartments in the larval trachea of Drosophila

eLife ◽

10.7554/elife.08666 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 9

Author(s):

Prashanth R Rao ◽

Li Lin ◽

Hai Huang ◽

Arjun Guha ◽

Sougata Roy ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Notch Signaling ◽

Clonal Analysis ◽

Border Cells ◽

Tracheal System ◽

Dorsal Branch ◽

Dividing Cells ◽

Organizational Feature ◽

Third Instar Larvae

The Drosophila tracheal system is a branched tubular network that forms in the embryo by a post-mitotic program of morphogenesis. In third instar larvae (L3), cells constituting the second tracheal metamere (Tr2) reenter the cell cycle. Clonal analysis of L3 Tr2 revealed that dividing cells in the dorsal trunk, dorsal branch and transverse connective branches respect lineage restriction boundaries near branch junctions. These boundaries corresponded to domains of gene expression, for example where cells expressing Spalt, Delta and Serrate in the dorsal trunk meet vein–expressing cells in the dorsal branch or transverse connective. Notch signaling was activated to one side of these borders and was required for the identity, specializations and segregation of border cells. These findings suggest that Tr2 is comprised of developmental compartments and that developmental compartments are an organizational feature relevant to branched tubular networks.

Download Full-text

Acheate-scute like 1 (Ascl1) is required for normal delta-like (Dll) gene expression and notch signaling during retinal development

Developmental Dynamics ◽

10.1002/dvdy.21848 ◽

2009 ◽

Vol 238 (9) ◽

pp. 2163-2178 ◽

Cited By ~ 50

Author(s):

Branden R. Nelson ◽

Byron H. Hartman ◽

Catherine A. Ray ◽

Toshinori Hayashi ◽

Olivia Bermingham-McDonogh ◽

...

Keyword(s):

Gene Expression ◽

Notch Signaling ◽

Retinal Development

Download Full-text

Possible Selective Cytotoxicity of Vanadium Complex on Breast Cancer Cells Involving Pathophysiological Pathways

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666191024122117 ◽

2020 ◽

Vol 19 (17) ◽

pp. 2130-2139 ◽

Cited By ~ 2

Author(s):

Eman S. El-Shafey ◽

Eslam S. Elsherbiny

Keyword(s):

Gene Expression ◽

Cell Death ◽

Notch Signaling ◽

Cancer Cells ◽

Signaling Pathways ◽

Caspase 3 ◽

Therapeutic Agent ◽

Notch Pathway ◽

Vanadium Complex ◽

Dependent Manner

Background: Triple-Negative Breast Cancers (TNBC) are among the most aggressive and therapyresistant breast tumors. Development of new treatment strategies that target pathways involved in cancer cells resistance is an attractive candidate to overcome therapeutic resistance. Objective: To clarify the antitumor activity of [VO (bpy)2 Cl] Cl complex as a new therapeutic agent through studying the interplay between apoptosis, autophagy and notch signaling pathways. Methods: Proliferation of MDA-MB-231 cells and IC50 value of the vanadium complex were assessed by MTT assay. Flow cytometry was utilized to detect cell cycle distribution, apoptosis assay, LC3 levels and Acid Vascular Organelles (AVOs). Caspase 3 levels were detected by ELISA. Changes in Notch1 gene expression were assessed by real-time PCR. AVOs qualitative detection was assessed by a fluorescence microscope. Results: The growth of MDA-MB-231 cells was suppressed after treatment with [VO (bpy)2 Cl] Cl complex, in a dose-dependent manner. The affinity for apoptotic cell death induction was shown through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase 3 levels. The affinity for autophagic cell death induction was observed through the increase in the G0/G1 phase, G2/M arrest, the increase of AVOs red fluorescence and elevated LC3 levels. The affinity for notch pathway inhibition was shown through the suppression of Notch 1 gene expression. Conclusion: [VO (bpy)2 Cl] Cl complex could be a promising candidate as therapeutic agent targeting different therapeutic targets including apoptosis, autophagy and notch signaling pathways.

Download Full-text