Notch pathway gene expression and wool follicle cell fates

2008 ◽  
Vol 48 (5) ◽  
pp. 648 ◽  
Author(s):  
Clare Gordon-Thomson ◽  
Steven A. Botto ◽  
Graham R. Cam ◽  
G. Philip M. Moore
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Notch Pathway ◽  
Cell Subpopulation ◽  
Cell Fates ◽  
Fetal Sheep ◽  
Pathway Gene ◽  
Wool Follicle ◽  
In Cells

The Notch family of genes has been implicated in specifying cell fates during hair follicle morphogenesis. We examined Notch gene expression during wool follicle formation, as an understanding of genes that influence cell distributions in the developing follicle is a prerequisite for devising molecular strategies to manipulate fibre characters and follicle density. We identified transcripts for the Notch1 receptor and one of its ligands, Jagged1, in fetal sheep skin by reverse transcriptase polymerase chain reaction. The sheep-specific cDNA sequences were used as templates to produce probes to investigate the expression patterns of Notch1 and Jagged1 in developing ovine fetal skin by in situ hybridisation. Notch1 and Jagged1 were detected in the epidermis and in a subpopulation of mesenchymal cells before follicle initiation. At day 70 during follicle initiation, transcripts were also detected in cells at the tip of the epidermal plug and in dermal condensates. By day 86, Notch1 and Jagged1 were detected in the distal cells of the epidermal downgrowths and epidermis and Notch1 was no longer detected in the mesenchyme and dermal condensates. After day 96, transcripts were absent from the epidermis, but localised to differentiating outer root sheath (ORS) cells. The distributions of transcripts implicate a Notch1–Jagged1 signal pathway in the fates of prospective ORS cells. The transient appearance of Notch1 in cells at the epidermal–mesenchymal junction during early follicle morphogenesis suggests that the receptor may be responsible for the specification of a cell subpopulation committed to a prepapilla fate at initiation.

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

Development ◽  
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.

Differential gene expression in activated monocyte-derived macrophages following binding of factor VIIa to tissue factor

2005 ◽  
Vol 94 (11) ◽  
pp. 1028-1034 ◽  
Author(s):  
Heidrun Muth ◽  
Ingo Kreis ◽  
Rene Zimmermann ◽  
Harald Tillmanns ◽  
Hans Hölschermann
Keyword(s):  
Gene Expression ◽  
Tissue Factor ◽  
Factor Viia ◽  
Expression Patterns ◽  
Leukocyte Recruitment ◽  
Coagulation Cascade ◽  
Array Analysis ◽  
Inflammatory Conditions ◽  
Coagulation Proteins ◽  
In Cells

SummaryFactor VIIa/tissue factor (FVIIa/TF) interaction has been reported to induce intracellular signalling in cells constitutively expressing TF, independently of downstream activation of the coagulation cascade. It is unknown, however, whether binding of FVII to its cofactor TF alters the gene expression profile in cells which inducible express TF under inflammatory conditions. To address this issue, gene expression patterns in cultured LPSstimulated monocyte-derived macrophages with or without exposure to FVIIa were compared by cDNA macro-array analysis. Of the 1176 genes examined on the array, a small set of six genes (IL-6, IL-8, TNF-a, GRO-beta alpha-thymosin, cathepsin H) were consistently up-regulated and one gene suppressed (alpha-antitrypsin) in response to FVIIa in activated monocyte-derived macrophages. Among the seven genes identified by array analysis, five genes were finally confirmed by real-time RT-PCR. Interestingly, all of these genes differentially regulated in response to FVIIa (GRO-beta, IL-6, IL-8, TNF-α and alpha-antitrypsin) are critical in inflammation. The changes in gene expression were reflected by corresponding changes in the protein concentrations of IL-6 and IL-8 as demonstrated by ELISA. Active site-inhibited FVIIa had no effect on gene expression indicating that FVIIa-induced gene alteration is dependent on the proteolytic activity of FVIIa. The FVIIa-induced alterations in gene expression were found to be TF-dependent but independent of downstream coagulation proteins like thrombin and FXa. In summary, this study demonstrates that binding of FVIIa to its cofactor TF enhances restricted pro-inflammatory genes in activated monocyte-derived macrophages. By up-regulation of chemokines critical for leukocyte recruitment, FVIIa/TF interaction on activated monocyte- derived macrophages could be relevant to prepare monocytes/ macrophages for extravasation and may represent a novel amplification loop of leukocyte recruitment.

scholarly journals Developmental Variation in Fruit Polyphenol Content and Related Gene Expression of a Red-Fruited versus a White-Fruited Fragaria vesca Genotype

Horticulturae ◽  
2018 ◽  
Vol 4 (4) ◽  
pp. 30
Author(s):  
Sutapa Roy ◽  
Sanjay Singh ◽  
Douglas Archbold
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Fruit Development ◽  
Biosynthetic Pathway ◽  
Receptor Gene ◽  
Expression Patterns ◽  
Related Gene ◽  
Pathway Gene ◽  
Fruit Development And Ripening ◽  
Flavonoid Biosynthetic Pathway

Two cultivars of F. vesca, red-fruited Baron Solemacher (BS) and white-fruited Pineapple Crush (PC), were studied to compare and contrast the quantitative accumulation of major polyphenols and related biosynthetic pathway gene expression patterns during fruit development and ripening. Developing PC fruit showed higher levels of hydroxycinnamic acids in green stages and a greater accumulation of ellagitannins in ripe fruit in comparison to BS. In addition to anthocyanin, red BS fruit had greater levels of flavan-3-ols when ripe than PC. Expression patterns of key structural genes and transcription factors of the phenylpropanoid/flavonoid biosynthetic pathway, an abscisic acid (ABA) biosynthetic gene, and a putative ABA receptor gene that may regulate the pathway, were also analyzed during fruit development and ripening to determine which genes exhibited differences in expression and when such differences were first evident. Expression of all pathway genes differed between the red BS and white PC at one or more times during development, most notably at ripening when phenylalanine ammonia lyase 1 (PAL1), chalcone synthase (CHS), flavanone-3′-hydroxylase (F3′H), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS), and UDP:flavonoid-O-glucosyltransferase 1 (UFGT1) were significantly upregulated in the red BS fruit. The transcription factors MYB1 and MYB10 did not differ substantially between red and white fruit except at ripening, when both the putative repressor MYB1 and promoter MYB10 were upregulated in red BS but not white PC fruit. The expression of ABA-related gene 9-cis-epoxycarotenoid dioxygenase 1 (NCED1) was higher in red BS fruit but only in the early green stages of development. Thus, a multigenic effect at several points in the phenylpropanoid/flavonoid biosynthetic pathway due to lack of MYB10 upregulation may have resulted in white PC fruit.

scholarly journals Precision of Tissue Patterning is Controlled by Dynamical Properties of Gene Regulatory Networks

2019 ◽  
Author(s):  
Katherine Exelby ◽  
Edgar Herrera-Delgado ◽  
Lorena Garcia Perez ◽  
Ruben Perez-Carrasco ◽  
Andreas Sagner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Cell Fates ◽  
Gene Circuits ◽  
Stochastic Fluctuations ◽  
Network Properties ◽  
Gene Regulatory

AbstractDuring development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.

scholarly journals A multiscale model of complex endothelial cell dynamics in early angiogenesis

2021 ◽  
Vol 17 (1) ◽  
pp. e1008055
Author(s):  
Daria Stepanova ◽  
Helen M. Byrne ◽  
Philip K. Maini ◽  
Tomás Alarcón
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Experimental Studies ◽  
Notch Pathway ◽  
Local Environment ◽  
Multiscale Model ◽  
Vascular Network ◽  
Border Effect ◽  
Potential Biomarker ◽  
The Impact

We introduce a hybrid two-dimensional multiscale model of angiogenesis, the process by which endothelial cells (ECs) migrate from a pre-existing vascular bed in response to local environmental cues and cell-cell interactions, to create a new vascular network. Recent experimental studies have highlighted a central role of cell rearrangements in the formation of angiogenic networks. Our model accounts for this phenomenon via the heterogeneous response of ECs to their microenvironment. These cell rearrangements, in turn, dynamically remodel the local environment. The model reproduces characteristic features of angiogenic sprouting that include branching, chemotactic sensitivity, the brush border effect, and cell mixing. These properties, rather than being hardwired into the model, emerge naturally from the gene expression patterns of individual cells. After calibrating and validating our model against experimental data, we use it to predict how the structure of the vascular network changes as the baseline gene expression levels of the VEGF-Delta-Notch pathway, and the composition of the extracellular environment, vary. In order to investigate the impact of cell rearrangements on the vascular network structure, we introduce the mixing measure, a scalar metric that quantifies cell mixing as the vascular network grows. We calculate the mixing measure for the simulated vascular networks generated by ECs of different lineages (wild type cells and mutant cells with impaired expression of a specific receptor). Our results show that the time evolution of the mixing measure is directly correlated to the generic features of the vascular branching pattern, thus, supporting the hypothesis that cell rearrangements play an essential role in sprouting angiogenesis. Furthermore, we predict that lower cell rearrangement leads to an imbalance between branching and sprout elongation. Since the computation of this statistic requires only individual cell trajectories, it can be computed for networks generated in biological experiments, making it a potential biomarker for pathological angiogenesis.

Molecular Classification of Multiple Myeloma (MM) Based on Gene Expression Profiling (GEP) and Fluorescence In Situ Hybridisation (FISH) Is an Independent Predictor for Event Free Survival (EFS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 507-507
Author(s):  
Dirk Hose ◽  
Jean-François Rossi ◽  
Carina Ittrich ◽  
John De Vos ◽  
Thierry Rème ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Molecular Classification ◽  
Rank Test ◽  
High Dose ◽  
Fluorescence In Situ Hybridisation ◽  
Prognostic Parameters ◽  
Log Rank Test

Abstract AIM was to test the new molecular classification of MM based on changes in global gene expression attributable to cytogenetic aberrations detected by interphase FISH (iFISH) in order to (i) predict EFS in a group of 100 MM-patients treated by high dose chemotherapy, and (ii) to investigate whether the classification represents an independent prognostic factor. PATIENTS AND METHODS. Bone marrow aspirates from MM-patients and normal donors were CD138-purified by magnetic activated cell sorting. RNA was in-vitro transcribed and hybridised to Affymetrix HG U133 A+B GeneChip (TG) and HG U133 2.0 plus array (VG). CCND1, CCND2 and FGFR3 expression was verified by real time RT-PCR and western blotting. iFISH was performed on purified MM-cells using probes for chromosomes 11q23, 13q14, 17p13 and the IgH-translocations t(4;14)(p16;q32.3) and t(11;14)(q13;q32.3). Expression data were normalised (Bioconductor package gcrma), and nearest shrunken centroids (NSC) applied to calculate and cross validate a predictor on a training group (TG) of 40 patients in whom a comprehensive iFISH panel combined with data on CCND overexpression were available. The ExpressMiner tool of the HUSAR bioinformatics laboratory was used to analyze genes differentially expressed between GEP-defined groups. A log-rank test and a Cox proportional hazard model were used to test the influence of prognostic parameters in combination with the predicted groups. RESULTS. Four groups were distinguished: (1.1) CCND1 (11q13) overexpression and trisomy 11q13, (1.2) CCND1 overexpression and translocations involving 11q13, i.e. t(11;14), (2.1) CCND2 overexpression without 11q13+, t(11;14), t(4;14), (2.2) CCND2 overexpression with t(4;14) and FGFR3 upregulation. A predictor of 6 genes correctly classified all 40 patients of the TG (estimated cross validated error rate 0%). An independent validation group (VG) of 65 patients was used. Distribution of clinical parameters (i.e. beta2M, Durie Salmon stages, ISS) was not significantly different between the 4 groups. The groups defined by the predictor have a significantly different EFS after autologous stem cell transplantation according to the GMMG-HD3 protocol (n=100; median: 26 /not reached /22 /6 months in groups 1.1 /1.2 /2.1 /2.2, respectively). A model testing the combination of the predicted group and B2M (above or below 3.5 mg/dl) showed a significant (p<0.006, log-rank-test) correlation with EFS. The distribution of del(13q14) (n=118) was (1.1) 34.0%, (1.2) 60.8%, (2.1) 46.4% and (2.2) 94%. The presence of a del(13q14) either in a subclone (<60% of analyzed nuclei) or major clone had no significant influence on EFS. CONCLUSION. Gene expression and iFISH allow a molecular classification of MM which can be predicted by GEP. Groups in the classification have distinct gene expression patterns as well as statistically significant different EFS. GEP-defined groups and B2M represent independent prognostic parameters.

Physical activity and prostate gene expression in men with low-risk prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 189-189 ◽  
Author(s):  
Mark Jesus Mendoza Magbanua ◽  
Erin L Richman ◽  
Eduardo V Sosa ◽  
Lee Jones ◽  
Jeffrey Simko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Low Risk ◽  
Normal Prostate ◽  
Pathway Gene ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

189 Background: Physical activity (PA), in particular longer duration or higher intensity, may reduce the risk of PCa progression and PCa-specific mortality in men diagnosed with clinically localized PCa. However, the molecular mechanism(s) by which PA exerts its protective effect in the prostate remains unknown. We examined the correlation of PA and gene expression patterns in men with low risk prostate cancer who elected to undergo active surveillance. Methods: Morphologically normal prostate tissue was obtained from men who subsequently participated in a clinical trial focused on nutritional supplements (previously published microarray dataset #GSE27140). Of the original sample (n=84), 70 completed a brief PA questionnaire and were dichotomized based usual PA [e.g. any vigorous PA (yes/no), 3+ h/wk vigorous PA (yes/no)]. Differential expression and pathway (gene set) analyses between groups were performed using Significance Analysis of Microarrays. Genes and gene sets with a false discovery rate ≤0.10 and 0.20 were considered significant, respectively. Results: Gene expression analysis detected 184 significant genes that were differentially expressed between men who performed vigorous PA for 3+ h/wk (n=23) and those who did not (n= 47). Up-regulated genes included the known tumor suppressors, BRCA1 and BRCA2. Furthermore, pathway analysis revealed that cell cycle and DNA repair pathways were positively modulated in men who participated in 3+h/wk vigorous PA vs. not. Consistent with the data on vigorous PA and clinical outcomes in men with PCa, the duration of vigorous PA was important; there were no significant genes detected when comparing men who participated in any vigorous PA to men who did none. Conclusions: Prostate gene expression and pathway analyses revealed candidate genes and in vivo pathways that may be modulated by participating in 3+ h/wk of vigorous PA. These data provide mechanistic insight into how 3+ h/wk of vigorous PA may offer PCa-specific benefits. Furthermore, understanding the molecular mechanisms by which such PA affects normal prostate gene expression may aid the development of strategies to prevent or delay PCa progression.

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