scholarly journals Expression of (beta)-catenin in the developing chick myotome is regulated by myogenic signals

Development ◽  
2000 ◽  
Vol 127 (19) ◽  
pp. 4105-4113
Author(s):  
M. Schmidt ◽  
M. Tanaka ◽  
A. Munsterberg
Keyword(s):  
Gene Expression ◽  
Wnt Pathway ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Specific Gene ◽  
Beta Catenin ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Cell Specification ◽  
Myogenic Precursor

The developmental signals that govern cell specification and differentiation in vertebrate somites are well understood. However, little is known about the downstream signalling pathways involved. We have shown previously that a combination of Shh protein and Wnt1 or Wnt3a-expressing fibroblasts is sufficient to activate skeletal muscle-specific gene expression in somite explants. Here, we have examined the molecular mechanisms by which the Wnt-mediated signal acts on myogenic precursor cells. We show that chick frizzled 1 (Fz1), beta-catenin and Lef1 are expressed during somitogenesis. Lef1 and beta-catenin transcripts become restricted to the developing myotome. Furthermore, beta-catenin is expressed prior to the time at which MyoD transcripts can be detected. Expression of beta-catenin mRNA is regulated by positive and negative signals derived from neural tube, notochord and lateral plate mesoderm. These signals include Bmp4, Shh and Wnt1/Wnt3a itself. In somite explants, Fz1, beta-catenin and Lef1 are expressed prior to activation of myogenesis in response to Shh and Wnt signals. Thus, our data show that a combination of Shh and Wnt1 upregulates expression of Wnt pathway components in developing somites prior to myogenesis. Thus, Wnt1 could act through beta-catenin on cells in the myotome.

Serial analysis of gene expression (SAGE) during porcine embryo development

2004 ◽  
Vol 16 (2) ◽  
pp. 87 ◽  
Author(s):  
Le Ann Blomberg ◽  
Kurt A. Zuelke
Keyword(s):  
Gene Expression ◽  
Functional Genomics ◽  
Embryo Development ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Transgenic Animals ◽  
Specific Gene ◽  
Research Strategies

Functional genomics provides a powerful means for delving into the molecular mechanisms involved in pre-implantation development of porcine embryos. High rates of embryonic mortality (30%), following either natural mating or artificial insemination, emphasise the need to improve the efficiency of reproduction in the pig. The poor success rate of live offspring from in vitro-manipulated pig embryos also hampers efforts to generate transgenic animals for biotechnology applications. Previous analysis of differential gene expression has demonstrated stage-specific gene expression for in vivo-derived embryos and altered gene expression for in vitro-derived embryos. However, the methods used to date examine relatively few genes simultaneously and, thus, provide an incomplete glimpse of the physiological role of these genes during embryogenesis. The present review will focus on two aspects of applying functional genomics research strategies for analysing the expression of genes during elongation of pig embryos between gestational day (D) 11 and D12. First, we compare and contrast current methodologies that are being used for gene discovery and expression analysis during pig embryo development. Second, we establish a paradigm for applying serial analysis of gene expression as a functional genomics tool to obtain preliminary information essential for discovering the physiological mechanisms by which distinct embryonic phenotypes are derived.

scholarly journals Antagonistic interactions in the zebrafish midline prior to the emergence of asymmetric gene expression are important for left–right patterning

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150402 ◽  
Author(s):  
Rebecca D. Burdine ◽  
Daniel T. Grimes
Keyword(s):  
Gene Expression ◽  
Lateral Plate Mesoderm ◽  
Internal Organs ◽  
Lateral Plate ◽  
Left Right Asymmetry ◽  
Antagonistic Interactions

Left–right (L-R) asymmetry of the internal organs of vertebrates is presaged by domains of asymmetric gene expression in the lateral plate mesoderm (LPM) during somitogenesis. Ciliated L-R coordinators (LRCs) are critical for biasing the initiation of asymmetrically expressed genes, such as nodal and pitx2 , to the left LPM. Other midline structures, including the notochord and floorplate, are then required to maintain these asymmetries. Here we report an unexpected role for the zebrafish EGF-CFC gene one-eyed pinhead ( oep ) in the midline to promote pitx2 expression in the LPM. Late zygotic oep (LZ oep ) mutants have strongly reduced or absent pitx2 expression in the LPM, but this expression can be rescued to strong levels by restoring oep in midline structures only. Furthermore, removing midline structures from LZ oep embryos can rescue pitx2 expression in the LPM, suggesting the midline is a source of an LPM pitx2 repressor that is itself inhibited by oep . Reducing lefty1 activity in LZ oep embryos mimics removal of the midline, implicating lefty1 in the midline-derived repression. Together, this suggests a model where Oep in the midline functions to overcome a midline-derived repressor, involving lefty1 , to allow for the expression of left side-specific genes in the LPM. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals Identification of biological pathways and genes associated with neurogenic heterotopic ossification by text mining

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8276 ◽  
Author(s):  
Yichong Zhang ◽  
Yuanbo Zhan ◽  
Yuhui Kou ◽  
Xiaofeng Yin ◽  
Yanhua Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Text Mining ◽  
Heterotopic Ossification ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Egf Receptor ◽  
Enrichment Analysis ◽  
Biological Pathways ◽  
Specific Gene ◽  
Cord Injury

Background Neurogenic heterotopic ossification is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury (SCI-TBI-HO). However, the underlying mechanisms of SCI-TBI-HO have proven difficult to elucidate. The aim of the present study is to identify the most promising candidate genes and biological pathways for SCI-TBI-HO. Methods In this study, we used text mining to generate potential explanations for SCI-TBI-HO. Moreover, we employed several additional datasets, including gene expression profile data, drug data and tissue-specific gene expression data, to explore promising genes that associated with SCI-TBI-HO. Results We identified four SCI-TBI-HO-associated genes, including GDF15, LDLR, CCL2, and CLU. Finally, using enrichment analysis, we identified several pathways, including integrin signaling, insulin pathway, internalization of ErbB1, urokinase-type plasminogen activator and uPAR-mediated signaling, PDGFR-beta signaling pathway, EGF receptor (ErbB1) signaling pathway, and class I PI3K signaling events, which may be associated with SCI-TBI-HO. Conclusions These results enhance our understanding of the molecular mechanisms of SCI-TBI-HO and offer new leads for researchers and innovative therapeutic strategies.

scholarly journals Convergent evolution of venom gland transcriptomes across Metazoa

2021 ◽  
Author(s):  
Giulia Zancolli ◽  
Maarten Reijnders ◽  
Robert Waterhouse ◽  
Marc Robinson-Rechavi
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Venom Gland ◽  
Bioactive Molecules ◽  
Specific Gene ◽  
Animal Kingdom ◽  
Venom Glands

Animals have repeatedly evolved specialized organs and anatomical structures to produce and deliver a cocktail of potent bioactive molecules to subdue prey or predators: venom. This makes it one of the most widespread convergent functions in the animal kingdom. Whether animals have adopted the same genetic toolkit to evolved venom systems is a fascinating question that still eludes us. Here, we performed the first comparative analysis of venom gland transcriptomes from 20 venomous species spanning the main Metazoan lineages, to test whether different animals have independently adopted similar molecular mechanisms to perform the same function. We found a strong convergence in gene expression profiles, with venom glands being more similar to each other than to any other tissue from the same species, and their differences closely mirroring the species phylogeny. Although venom glands secrete some of the fastest evolving molecules (toxins), their gene expression does not evolve faster than evolutionarily older tissues. We found 15 venom gland specific gene modules enriched in endoplasmic reticulum stress and unfolded protein response pathways, indicating that animals have independently adopted stress response mechanisms to cope with mass production of toxins. This, in turns, activates regulatory networks for epithelial development, cell turnover and maintenance which seem composed of both convergent and lineage-specific factors, possibly reflecting the different developmental origins of venom glands. This study represents the first step towards an understanding of the molecular mechanisms underlying the repeated evolution of one of the most successful adaptive traits in the animal kingdom.

A Wnt signaling pathway controls hox gene expression and neuroblast migration in C. elegans

Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 37-49 ◽  
Author(s):  
J.N. Maloof ◽  
J. Whangbo ◽  
J.M. Harris ◽  
G.D. Jongeward ◽  
C. Kenyon
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Hox Genes ◽  
Wnt Signaling Pathway ◽  
Beta Catenin ◽  
Hox Gene ◽  
C Elegans ◽  
Neuroblast Migration ◽  
Pathway Gene

The specification of body pattern along the anteroposterior (A/P) body axis is achieved largely by the actions of conserved clusters of Hox genes. Limiting expression of these genes to localized regional domains and controlling the precise patterns of expression within those domains is critically important for normal patterning. Here we report that egl-20, a C. elegans gene required to activate expression of the Hox gene mab-5 in the migratory neuroblast QL, encodes a member of the Wnt family of secreted glycoproteins. We have found that a second Wnt pathway gene, bar-1, which encodes a beta-catenin/Armadillo-like protein, is also required for activation of mab-5 expression in QL. In addition, we describe the gene pry-1, which is required to limit expression of the Hox genes lin-39, mab-5 and egl-5 to their correct local domains. We find that egl-20, pry-1 and bar-1 all function in a linear genetic pathway with conserved Wnt signaling components, suggesting that a conserved Wnt pathway activates expression of mab-5 in the migratory neuroblast QL. Moreover, we find that members of this Wnt signaling system play a major role in both the general and fine-scale control of Hox gene expression in other cell types along the A/P axis.

scholarly journals Analyses of Avascular Mutants Reveal Unique Transcriptomic Signature of Non-conventional Endothelial Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Boryeong Pak ◽  
Christopher E. Schmitt ◽  
Woosoung Choi ◽  
Jun-Dae Kim ◽  
Orjin Han ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Lineage Tracing ◽  
Molecular Characteristics ◽  
Lateral Plate Mesoderm ◽  
Rna Seq ◽  
Developmental History ◽  
Lateral Plate ◽  
Developmental Origin ◽  
Transcriptomic Signature

Endothelial cells appear to emerge from diverse progenitors. However, to which extent their developmental origin contributes to define their cellular and molecular characteristics remains largely unknown. Here, we report that a subset of endothelial cells that emerge from the tailbud possess unique molecular characteristics that set them apart from stereotypical lateral plate mesoderm (LPM)-derived endothelial cells. Lineage tracing shows that these tailbud-derived endothelial cells arise at mid-somitogenesis stages, and surprisingly do not require Npas4l or Etsrp function, indicating that they have distinct spatiotemporal origins and are regulated by distinct molecular mechanisms. Microarray and single cell RNA-seq analyses reveal that somitogenesis- and neurogenesis-associated transcripts are over-represented in these tailbud-derived endothelial cells, suggesting that they possess a unique transcriptomic signature. Taken together, our results further reveal the diversity of endothelial cells with respect to their developmental origin and molecular properties, and provide compelling evidence that the molecular characteristics of endothelial cells may reflect their distinct developmental history.

Expression of a growth arrest specific gene (gas-6) during liver regeneration: Molecular mechanisms and signalling pathways

1994 ◽  
Vol 158 (2) ◽  
pp. 263-269 ◽  
Author(s):  
Marina Ferrero ◽  
Maria Alfonsina Desiderio ◽  
Alessia Martinotti ◽  
Cecilia Melani ◽  
Aldo Bernelli-Zazzera ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Molecular Mechanisms ◽  
Growth Arrest ◽  
Signalling Pathways ◽  
Specific Gene

scholarly journals The Repressor Element 1-Silencing Transcription Factor Regulates Heart-Specific Gene Expression Using Multiple Chromatin-Modifying Complexes

2007 ◽  
Vol 27 (11) ◽  
pp. 4082-4092 ◽  
Author(s):  
Andrew J. Bingham ◽  
Lezanne Ooi ◽  
Lukasz Kozera ◽  
Edward White ◽  
Ian C. Wood
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cardiac Hypertrophy ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Ventricular Myocytes ◽  
Specific Gene ◽  
Histone H4 Acetylation ◽  
Repressor Element

ABSTRACT Cardiac hypertrophy is associated with a dramatic change in the gene expression profile of cardiac myocytes. Many genes important during development of the fetal heart but repressed in the adult tissue are reexpressed, resulting in gross physiological changes that lead to arrhythmias, cardiac failure, and sudden death. One transcription factor thought to be important in repressing the expression of fetal genes in the adult heart is the transcriptional repressor REST (repressor element 1-silencing transcription factor). Although REST has been shown to repress several fetal cardiac genes and inhibition of REST function is sufficient to induce cardiac hypertrophy, the molecular mechanisms employed in this repression are not known. Here we show that continued REST expression prevents increases in the levels of the BNP (Nppb) and ANP (Nppa) genes, encoding brain and atrial natriuretic peptides, in adult rat ventricular myocytes in response to endothelin-1 and that inhibition of REST results in increased expression of these genes in H9c2 cells. Increased expression of Nppb and Nppa correlates with increased histone H4 acetylation and histone H3 lysine 4 methylation of promoter-proximal regions of these genes. Furthermore, using deletions of individual REST repression domains, we show that the combined activities of two domains of REST are required to efficiently repress transcription of the Nppb gene; however, a single repression domain is sufficient to repress the Nppa gene. These data provide some of the first insights into the molecular mechanism that may be important for the changes in gene expression profile seen in cardiac hypertrophy.

Sensitivity to Wnt Pathway Inhibition in CLL Is Associated with Specific Gene Expression Signatures

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 801-801
Author(s):  
Lili Wang ◽  
Alex K Shalek ◽  
Jellert Gaublomme ◽  
Nir Yosef ◽  
Jennifer R Brown ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Cell Viability ◽  
B Cell ◽  
Cell Survival ◽  
Wnt Pathway ◽  
Differentially Expressed ◽  
Differential Sensitivity ◽  
Specific Gene ◽  
Disease Heterogeneity

Abstract Abstract 801 We have recently found that the Wnt/b-catenin signaling pathway plays a key role in chronic lymphocytic leukemia (CLL). We were, however, intrigued by the question of whether this aberrant pathway may function differently in independent leukemias, and contribute to disease heterogeneity. To assess differential activity of the Wnt pathway across patients, we tested the effects of blocking Wnt activation on CLL cell survival. We knocked down a key downstream gene, LEF1, which is the most differentially expressed gene in CLL compared to normal B cells (based on gene expression microarrays). Addressing this question requires genetic manipulation of primary normal and malignant human B cells, and yet these cells are notoriously difficult to transfect. We therefore focused on developing a method for introducing siRNAs into normal and malignant B cells. We adapted a novel delivery system consisting of vertical silicon nanowires (SiNWs, Shalek et al PNAS 2010) that penetrate the plasma membrane in a minimally invasive fashion and deliver biomolecular cargo directly into the cytoplasm. We achieved consistent and reliable delivery of fluorescently labeled siRNAs (at 50–200 pmol) into normal and CLL B cells. siRNA was delivered to >90% of cells with >85% cell viability remaining after 48 hours. We used this platform to knockdown LEF1 in 20 CLL-B and 5 normal CD19+ B cell samples, and examined cell survival 48 hours after siRNA delivery using an ATP-based CellTiter-Glo assay. Indeed, our studies revealed a heterogeneous response among CLL-B cells to LEF1 inhibition. As a group, CLL-B cells were significantly more sensitive to LEF1 knockdown with a survival rate of 77% (12% s.e.m) compared to 97% (13% s.e.m) in normal B cells. CLL B cells from different patients showed differential sensitivity to LEF1 knockdown, with 8 non-responders, 8 intermediate responders and 4 strong responders (i.e. significant death). Sensitivity to LEF1 inhibition did not correlate with known CLL cytogenetic prognostic factors. To determine if the differential response to LEF1 knockdown was associated with specific gene signatures, we examined gene expression data generated from CLL-B cells from 12 (4 strong, 3 intermediate, and 5 non-responders) of the 20 CLLs tested (using the Affymetrix U133 Plus 2 Array). To increase statistical power, we used each CLL's expression profile (using only genes that showed variability across samples) to create clusters of ∼19 CLLs that showed similar expression profiles (using microarray data from our compendium of 177 additional CLLs). We further reduced the number of genes to ∼4000 genes by retaining only those whose expression levels were significantly different in at least one associated cluster relative to normal CD19+ B cell controls (T-test, FDR<10−4; p-values converted using the Benjamini-Hochberg method). These analyses led to the identification of several hundred genes whose expression correlated significantly with LEF1 knockdown's effect on cell viability. Analysis of these differentially expressed genes identified several potentially important pathways. Ongoing analyses include the identification and validation of a molecular signature for this effect. This signature could enable rapid identification of patients who would be most responsive to therapy with LEF1 inhibitors, which are under development along with other Wnt pathway inhibitors. Disclosures: No relevant conflicts of interest to declare.

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