scholarly journals Signaling Modulations of miR-206-3p in Tooth Morphogenesis

2020 ◽  
Vol 21 (15) ◽  
pp. 5251
Author(s):  
Sanjiv Neupane ◽  
Yam Prasad Aryal ◽  
Tae-Young Kim ◽  
Chang-Yeol Yeon ◽  
Chang-Hyeon An ◽  
...  

MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs that post-transcriptionally regulate gene expression in organisms. Most mammalian miRNAs influence biological processes, including developmental changes, tissue morphogenesis and the maintenance of tissue identity, cell growth, differentiation, apoptosis, and metabolism. The miR-206-3p has been correlated with cancer; however, developmental roles of this miRNA are unclear. In this study, we examined the expression pattern and evaluated the developmental regulation of miR-206-3p during tooth morphogenesis using ex-vivo culture method. The expression pattern of miR-206-3p was examined in the epithelium and mesenchyme of developing tooth germ with stage-specific manners. Perturbation of the expression of miR-206-3p clearly altered expression patterns of dental-development–related signaling molecules, including Axin2, Bmp2, Fgf4, Lef1 and Shh. The gene expression complemented with change in cellular events including, apoptosis and proliferation which caused altered crown and pulp morphogenesis in renal-capsule–calcified teeth. Especially, mislocalization of β-Catenin and SMAD1/5/8 were observed alongside dramatic alterations in the expression patterns of Fgf4 and Shh. Overall, our data suggest that the miR-206-3p regulate the cellular physiology during tooth morphogenesis through modulation of the Wnt, Bmp, Fgf, and Shh signaling pathways to form proper tooth pulp and crown.

2020 ◽  
Vol 21 (21) ◽  
pp. 8079
Author(s):  
Yam Prasad Aryal ◽  
Sanjiv Neupane ◽  
Tae-Young Kim ◽  
Eui-Seon Lee ◽  
Nitin Kumar Pokhrel ◽  
...  

FUSE binding protein 1 (Fubp1), a regulator of the c-Myc transcription factor and a DNA/RNA-binding protein, plays important roles in the regulation of gene transcription and cellular physiology. In this study, to reveal the precise developmental function of Fubp1, we examined the detailed expression pattern and developmental function of Fubp1 during tooth morphogenesis by RT-qPCR, in situ hybridization, and knock-down study using in vitro organ cultivation methods. In embryogenesis, Fubp1 is obviously expressed in the enamel organ and condensed mesenchyme, known to be important for proper tooth formation. Knocking down Fubp1 at E14 for two days, showed the altered expression patterns of tooth development related signalling molecules, including Bmps and Fgf4. In addition, transient knock-down of Fubp1 at E14 revealed changes in the localization patterns of c-Myc and cell proliferation in epithelium and mesenchyme, related with altered tooth morphogenesis. These results also showed the decreased amelogenin and dentin sialophosphoprotein expressions and disrupted enamel rod and interrod formation in one- and three-week renal transplanted teeth respectively. Thus, our results suggested that Fubp1 plays a modulating role during dentinogenesis and amelogenesis by regulating the expression pattern of signalling molecules to achieve the proper structural formation of hard tissue matrices and crown morphogenesis in mice molar development.


2007 ◽  
Vol 31 (3) ◽  
pp. 441-457 ◽  
Author(s):  
Miroslaw Mackiewicz ◽  
Keith R. Shockley ◽  
Micah A. Romer ◽  
Raymond J. Galante ◽  
John E. Zimmerman ◽  
...  

The function(s) of sleep remains a major unanswered question in biology. We assessed changes in gene expression in the mouse cerebral cortex and hypothalamus following different durations of sleep and periods of sleep deprivation. There were significant differences in gene expression between behavioral states; we identified 3,988 genes in the cerebral cortex and 823 genes in the hypothalamus with altered expression patterns between sleep and sleep deprivation. Changes in the steady-state level of transcripts for various genes are remarkably common during sleep, as 2,090 genes in the cerebral cortex and 409 genes in the hypothalamus were defined as sleep specific and changed (increased or decreased) their expression during sleep. The largest categories of overrepresented genes increasing expression with sleep were those involved in biosynthesis and transport. In both the cerebral cortex and hypothalamus, during sleep there was upregulation of multiple genes encoding various enzymes involved in cholesterol synthesis, as well as proteins for lipid transport. There was also upregulation during sleep of genes involved in synthesis of proteins, heme, and maintenance of vesicle pools, as well as antioxidant enzymes and genes encoding proteins of energy-regulating pathways. We postulate that during sleep there is a rebuilding of multiple key cellular components in preparation for subsequent wakefulness.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jorge A. Ramírez-Tejero ◽  
Jaime Jiménez-Ruiz ◽  
Alicia Serrano ◽  
Angjelina Belaj ◽  
Lorenzo León ◽  
...  

Abstract Background Olive orchards are threatened by a wide range of pathogens. Of these, Verticillium dahliae has been in the spotlight for its high incidence, the difficulty to control it and the few cultivars that has increased tolerance to the pathogen. Disease resistance not only depends on detection of pathogen invasion and induction of responses by the plant, but also on barriers to avoid the invasion and active resistance mechanisms constitutively expressed in the absence of the pathogen. In a previous work we found that two healthy non-infected plants from cultivars that differ in V. dahliae resistance such as ‘Frantoio’ (resistant) and ‘Picual’ (susceptible) had a different root morphology and gene expression pattern. In this work, we have addressed the issue of basal differences in the roots between Resistant and Susceptible cultivars. Results The gene expression pattern of roots from 29 olive cultivars with different degree of resistance/susceptibility to V. dahliae was analyzed by RNA-Seq. However, only the Highly Resistant and Extremely Susceptible cultivars showed significant differences in gene expression among various groups of cultivars. A set of 421 genes showing an inverse differential expression level between the Highly Resistant to Extremely Susceptible cultivars was found and analyzed. The main differences involved higher expression of a series of transcription factors and genes involved in processes of molecules importation to nucleus, plant defense genes and lower expression of root growth and development genes in Highly Resistant cultivars, while a reverse pattern in Moderately Susceptible and more pronounced in Extremely Susceptible cultivars were observed. Conclusion According to the different gene expression patterns, it seems that the roots of the Extremely Susceptible cultivars focus more on growth and development, while some other functions, such as defense against pathogens, have a higher expression level in roots of Highly Resistant cultivars. Therefore, it seems that there are constitutive differences in the roots between Resistant and Susceptible cultivars, and that susceptible roots seem to provide a more suitable environment for the pathogen than the resistant ones.


Author(s):  
Jieping Ye ◽  
Ravi Janardan ◽  
Sudhir Kumar

Understanding the roles of genes and their interactions is one of the central challenges in genome research. One popular approach is based on the analysis of microarray gene expression data (Golub et al., 1999; White, et al., 1999; Oshlack et al., 2007). By their very nature, these data often do not capture spatial patterns of individual gene expressions, which is accomplished by direct visualization of the presence or absence of gene products (mRNA or protein) (e.g., Tomancak et al., 2002; Christiansen et al., 2006). For instance, the gene expression pattern images of a Drosophila melanogaster embryo capture the spatial and temporal distribution of gene expression patterns at a given developmental stage (Bownes, 1975; Tsai et al., 1998; Myasnikova et al., 2002; Harmon et al., 2007). The identification of genes showing spatial overlaps in their expression patterns is fundamentally important to formulating and testing gene interaction hypotheses (Kumar et al., 2002; Tomancak et al., 2002; Gurunathan et al., 2004; Peng & Myers, 2004; Pan et al., 2006). Recent high-throughput experiments of Drosophila have produced over fifty thousand images (http://www. fruitfly.org/cgi-bin/ex/insitu.pl). It is thus desirable to design efficient computational approaches that can automatically retrieve images with overlapping expression patterns. There are two primary ways of accomplishing this task. In one approach, gene expression patterns are described using a controlled vocabulary, and images containing overlapping patterns are found based on the similarity of textual annotations. In the second approach, the most similar expression patterns are identified by a direct comparison of image content, emulating the visual inspection carried out by biologists [(Kumar et al., 2002); see also www.flyexpress.net]. The direct comparison of image content is expected to be complementary to, and more powerful than, the controlled vocabulary approach, because it is unlikely that all attributes of an expression pattern can be completely captured via textual descriptions. Hence, to facilitate the efficient and widespread use of such datasets, there is a significant need for sophisticated, high-performance, informatics-based solutions for the analysis of large collections of biological images.


2019 ◽  
Vol 87 (3) ◽  
pp. 485-493 ◽  
Author(s):  
Magdalena Zasada ◽  
Anna Madetko-Talowska ◽  
Cecilie Revhaug ◽  
Anne Gro W. Rognlien ◽  
Lars O. Baumbusch ◽  
...  

Abstract Background We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. Methods A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. Results There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. Conclusion There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1204-1204
Author(s):  
Lykke Christina Grubach ◽  
Mike Zangenberg ◽  
Hans Beier Ommen ◽  
Anni Aggerholm ◽  
Peter Hokland

Abstract INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous disease with varying survival rates depending mostly upon the molecular phenotype of the single leukemic clone. The most powerful predictor for the outcome of the individual patient is the cytogenetic profile at the time of diagnosis, dividing the patients into good, intermediate and adverse prognostic group. However, given that 40–60 percent of patients exhibits a normal karyotype and are assigned to an intermediate prognostic group, identification of biologic parameters, which either alone or in combination, predict disease outcome more precisely are needed. We have previously performed a gene expression profiling study (Grubach et al, Eur J. Hematol. 2008 Apr 10. [Epub ahead of print]) on a series of Polycomb, Hox and Meis genes expressed in hematopoietic cells. AIM: Based on the finding that HOXA4 could be used as a predictor for outcome in AML patients with a normal karyotype, we hypothesized that combining the gene expression of the HOXA4 gene and co-factor MEIS1 might unravel a leukemogenic impact in other cytogenetic prognostic groups (Grimwade et al. Blood. 1998 Oct 1;92(7):2322–33). In addition, given that epigenetic events might contribute to the regulation of these genes, we determined whether promoter hypermethylation of CpG islands in the promoter regions were of relevance to the expression levels of HOXA4 and MEIS1. MATERIALS & METHODS: Diagnosis samples from 248 AML patients were analyzed by RQ-PCR for expression levels of HOXA4 and MEIS1. 157 of these patients were further analyzed for promoter hypermethylation of the same genes by bisulphite treatment of DNA followed by methylation-specific melting curve analysis (MS-MCA). RESULTS: When combining the gene expression levels of HOXA4 with MEIS1 into the three main groups (low HOXA4/low MEIS1, low HOXA4/high MEIS1 and normal-high HOXA4/high MEIS1; (the latter pooled to enable statistical calculations)), clear differences in overall survival were found (Fig. 1). Thus, within the group of patients exhibiting low levels of HOXA4 transcript, those with a high expression of MEIS1 had a significantly worse outcome than those having low MEIS1 expression (p=0.025). Importantly, in a multiparameter regression analysis, the prediction was independent of the cytogenetic grouping, of mutations in NPM1 and FLT3 genes, WBC and age. Given the efficacy of demethylating therapy, we also considered the mechanism of HOXA4 and MEIS1 gene regulation. Thus, when promoter methylation of HOXA4 and MEIS1 in 157 patients was investigated, we found that 15 % of the patients had hypermethylation of the promoter region of MEIS1 and 77% of the patients showed hypermethylation of HOXA4. Importantly, a significant correlation for both of the genes between the expression level and methylation state was observed (MEIS1, p=0.001 and HOXA4, p=0.007). CONCLUSION: The altered expression levels of HOXA4 and MEIS1 in AML reflect, at least partly, an epigenetic regulation by virtue of promoter hypermethylation. The level of transcripts of HOXA4 and MEIS1 seem to contribute to the leukemogenesis in AML and can serve as independent prognostic variables regardless of their cytogenetic and molecular background. Fig. 1. Overall survival of AML patients-stratified by cytogenetics, mutations in NPM1 and FLT3, WBC and age. By combination of HOXA4 and Meis1 expression a significant better survival is linked to those with a low HOXA4/low MEIS1 compared to those with a low HOXA4/high MEIS1 expression. Fig. 1. Overall survival of AML patients-stratified by cytogenetics, mutations in NPM1 and FLT3, WBC and age. By combination of HOXA4 and Meis1 expression a significant better survival is linked to those with a low HOXA4/low MEIS1 compared to those with a low HOXA4/high MEIS1 expression.


2004 ◽  
Vol 52 (2) ◽  
pp. 135-141 ◽  
Author(s):  
H. Kocams¸ ◽  
N. Gulmez ◽  
S. Aslan ◽  
M. Nazlı

The objective of the present study was to determine the effects of follistatin addition on myostatin and follistatin gene expression patterns in C2C12 muscle cells. C2C12 cells were administered with 100 ng/ml recombinant human (rh) follistatin in Dulbecco's modified Eagle medium (DMEM) containing 10% fetal bovine serum (FBS), 4 mM glutamine and antibiotics daily for three days. Rh follistatin was not added in the control wells. Follistatin and myostatin gene cDNAs were synthesised by reverse transcriptase polymerase chain reaction (RT-PCR).The time course of follistatin gene expression pattern was similar in both the control and the follistatin-treated group. Myostatin mRNA level significantly increased in the follistatin-treated group after 24 h of culture (Fig. 3, P < 0.01). Amounts then sharply decreased (Fig. 3, P < 0.01) at 48 h of culture, whereas there was no significant difference between the control and the follistatin-treated group at 72 h of culture. Our results demonstrated that myostatin and follistatin mRNA were expressed in C2C12 cells and rh follistatin changed the myostatin expression pattern.


2021 ◽  
Vol 6 ◽  
pp. 197
Author(s):  
John C.W. Hildyard ◽  
Dominic J. Wells ◽  
Richard J. Piercy

Background: Progression through mammalian embryogenesis involves many interacting cell types and multiple differentiating cell lineages. Quantitative polymerase chain reaction (qPCR) analysis of gene expression in the developing embryo is a valuable tool for deciphering these processes, but normalisation to stably-expressed reference genes is essential for such analyses. Gene expression patterns change globally and dramatically as embryonic development proceeds, rendering identification of consistently appropriate reference genes challenging. Methods: We have investigated expression stability in mouse embryos from mid to late gestation (E11.5–E18.5), both at the whole-embryo level, and within the head and forelimb specifically, using 15 candidate reference genes (ACTB, 18S, SDHA, GAPDH, HTATSF1, CDC40, RPL13A, CSNK2A2, AP3D1, HPRT1, CYC1, EIF4A, UBC, B2M and PAK1IP1), and four complementary algorithms (geNorm, Normfinder, Bestkeeper and deltaCt). Results: Unexpectedly, all methods suggest that many genes within our candidate panel are acceptable references, though AP3D1, RPL13A and PAK1IP1 are the strongest performing genes overall. HPRT1 and B2M are conversely poor choices, and show strong developmental regulation. We further show that normalisation using our three highest-scoring references can reveal subtle patterns of developmental expression even in genes ostensibly ranked as acceptably stable (CDC40, HTATSF1). Conclusion: AP3D1, RPL13A and PAK1IP1 represent universally suitable reference genes for expression studies in the E11.5-E18.5 mouse embryo.


Science ◽  
2021 ◽  
Vol 371 (6527) ◽  
pp. 396-400 ◽  
Author(s):  
Charalampos Chrysovalantis Galouzis ◽  
Benjamin Prud’homme

Sexual dimorphism in animals results from sex-biased gene expression patterns. These patterns are controlled by genetic sex determination hierarchies that establish the sex of an individual. Here we show that the male-biased wing expression pattern of the Drosophila biarmipes gene yellow, located on the X chromosome, is independent of the fly sex determination hierarchy. Instead, we find that a regulatory interaction between yellow alleles on homologous chromosomes (a process known as transvection) silences the activity of a yellow enhancer functioning in the wing. Therefore, this enhancer can be active in males (XY) but not in females (XX). This transvection-dependent enhancer silencing requires the yellow intron and the chromatin architecture protein Mod(mdg4). Our results suggest that transvection can contribute more generally to the sex-biased expression of X-linked genes.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Hao Xie ◽  
Bo Li ◽  
Yu Chang ◽  
Xiaoyan Hou ◽  
Yue Zhang ◽  
...  

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is an accurate and convenient method for mRNA quantification. Selection of optimal reference gene(s) is an important step in RT-qPCR experiments. However, the stability of housekeeping genes in spinach (Spinacia oleracea) under various abiotic stresses is unclear. Evaluating the stability of candidate genes and determining the optimal gene(s) for normalization of gene expression in spinach are necessary to investigate the gene expression patterns during development and stress response. In this study, ten housekeeping genes, 18S ribosomal RNA (18S rRNA), actin, ADP ribosylation factor (ARF), cytochrome c oxidase subunit 5C (COX), cyclophilin (CYP), elongation factor 1-alpha (EF1α), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histone H3 (H3), 50S ribosomal protein L2 (RPL2), and tubulin alpha chain (TUBα) from spinach, were selected as candidates in roots, stems, leaves, flowers, and seedlings in response to high temperature, CdCl2, NaCl, NaHCO3, and Na2CO3 stresses. The expression of these genes was quantified by RT-qPCR and evaluated by NormFinder, BestKeeper, and geNorm. 18S rRNA, actin, ARF, COX, CYP, EF1α, GAPDH, H3, and RPL2 were detected as optimal reference genes for gene expression analysis of different organs and stress responses. The results were further confirmed by the expression pattern normalized with different reference genes of two heat-responsive genes. Here, we optimized the detection method of the gene expression pattern in spinach. Our results provide the optimal candidate reference genes which were crucial for RT-qPCR analysis.


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