scholarly journals Differential rescue of visceral and cardiac defects inDrosophilaby vertebratetinman-related genes

1998 ◽  
Vol 95 (16) ◽  
pp. 9366-9371 ◽  
Author(s):  
Maijon Park ◽  
Carol Lewis ◽  
David Turbay ◽  
Amy Chung ◽  
Jau-Nian Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Molecular Mechanisms ◽  
Marker Gene ◽  
Homeobox Gene ◽  
Specific Gene ◽  
Specific Marker ◽  
Cardiac Progenitors ◽  
Mesoderm Development ◽  
Visceral Mesoderm

tinman, a mesodermal NK2-type homeobox gene, is absolutely required for the subdivision of the earlyDrosophilamesoderm and for the formation of the heart as well as the visceral muscle primordia. Several vertebrate relatives oftinman, many of which are predominately expressed in the very early cardiac progenitors (and pharyngeal endoderm), also seem to promote heart development. Here, we show that most of these vertebratetinman-related genes can readily substitute forDrosophila tinmanfunction in promoting visceral mesoderm-specific marker gene expression, but much less in promoting cardiac-specific gene expression indicative of heart development. In addition, another mesodermal NK2-type gene fromDrosophila,bagpipe, which is normally only needed for visceral mesoderm but not heart development, cannot substitute fortinmanat all. These data indicate that the functional equivalence of thetinman-related subclass of NK2-type genes (in activating markers of visceral mesoderm development inDrosophila) is specific to this subclass and distinct from other homeobox genes. Despite the apparent overall conservation of heart development between vertebrates and invertebrates, the differential rescue of visceral mesoderm versus heart development suggests that some of the molecular mechanisms of organ formation may have diverged during evolution.

scholarly journals The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice

2006 ◽  
Vol 37 (2) ◽  
pp. 301-316 ◽  
Author(s):  
Andreas Petri ◽  
Jonas Ahnfelt-Rønne ◽  
Klaus Stensgaard Frederiksen ◽  
David George Edwards ◽  
Dennis Madsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Molecular Mechanisms ◽  
Homeobox Gene ◽  
Specific Gene ◽  
Wild Type ◽  
Specific Gene Expression ◽  
And Function ◽  
Deficient Mice

To understand the molecular mechanisms regulating pancreatic endocrine development and function, pancreatic gene expression was compared between Ngn3-deficient mice and littermate controls on embryonic days 13 and 15. Microarray analysis identified 504 genes with significant differences in expression. Fifty-two of these showed at least twofold reduction in Ngn3 knockouts compared to controls. Many of them were previously described to be involved in endocrine development and function. Among the genes not previously characterized were Rhomboid veinlet-like 4, genes involved in tetrahydrobiopterin biosynthesis and the Iroquois-type homeobox gene Irx1, the latter was selected for further investigation. In situ hybridisation demonstrated that two Iroquois genes, Irx1 and Irx2, were expressed in pancreatic endoderm of wild-type, but not Ngn3 mutant embryos. Furthermore, ectopic Ngn3 induced prominent Irx2 expression in chicken endoderm. Co-labelling established that Irx1 and Irx2 mRNA is located to glucagon-, but not insulin- or somatostatin-producing cells in mice and chicken. These data suggest that Irx1 and Irx2 serve an evolutionary conserved role in the regulation of α-cell-specific gene expression.

scholarly journals Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation

2013 ◽  
Vol 42 (5) ◽  
pp. 2958-2975 ◽  
Author(s):  
Ajeet Pratap Singh ◽  
Trevor K. Archer
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Chromatin Remodeling ◽  
Heart Development ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Affinity Purification ◽  
Specific Gene ◽  
Nucleosome Remodeling ◽  
Cardiac Gene

Abstract The regulatory networks of differentiation programs and the molecular mechanisms of lineage-specific gene regulation in mammalian embryos remain only partially defined. We document differential expression and temporal switching of BRG1-associated factor (BAF) subunits, core pluripotency factors and cardiac-specific genes during post-implantation development and subsequent early organogenesis. Using affinity purification of BRG1 ATPase coupled to mass spectrometry, we characterized the cardiac-enriched remodeling complexes present in E8.5 mouse embryos. The relative abundance and combinatorial assembly of the BAF subunits provides functional specificity to Switch/Sucrose NonFermentable (SWI/SNF) complexes resulting in a unique gene expression profile in the developing heart. Remarkably, the specific depletion of the BAF250a subunit demonstrated differential effects on cardiac-specific gene expression and resulted in arrhythmic contracting cardiomyocytes in vitro. Indeed, the BAF250a physically interacts and functionally cooperates with Nucleosome Remodeling and Histone Deacetylase (NURD) complex subunits to repressively regulate chromatin structure of the cardiac genes by switching open and poised chromatin marks associated with active and repressed gene expression. Finally, BAF250a expression modulates BRG1 occupancy at the loci of cardiac genes regulatory regions in P19 cell differentiation. These findings reveal specialized and novel cardiac-enriched SWI/SNF chromatin-remodeling complexes, which are required for heart formation and critical for cardiac gene expression regulation at the early stages of heart development.

scholarly journals A Benchmark of the Marker Gene Tool: MGFM

2017 ◽  
Vol 3 (1) ◽  
pp. 55
Author(s):  
Khadija El Amrani ◽  
Nancy Mah ◽  
Andreas Kurtz
Keyword(s):  
Gene Expression ◽  
Microarray Data ◽  
Molecular Mechanisms ◽  
Marker Gene ◽  
Genomic Research ◽  
Marker Genes ◽  
Tissue Cell ◽  
Specific Gene ◽  
Data Set ◽  
Tissue Specific

Large amounts of microarray experimental data are available in public repositories. Although a variety of tools have been developed to make use of these data, the number of tools that detect marker genes is limited. Identification of marker genes associated with a specific tissue/cell type is a fundamental challenge in genetic and genomic research. In addition to other genes, marker genes are of great importance for understanding the gene function, the molecular mechanisms underlying complex diseases, and may lead to the development of new drug targets. We have previously developed a Bioconductor R package (MGFM) for marker gene detection from microarray data. The tool is freely available from the Bioconductor web site (https://www.bioconductor.org/packages/release/bioc/html/MGFM.html), and it is also provided as an online application integrated into the CellFinder platform (http://cellfinder.org/analysis/marker). In this work, we applied our tool to a public microarray data set from the NCBI’s Gene Expression Omnibus public repository encompassing samples for 12 human tissues. We compared the set of predicted marker genes to a set of tissue-specific genes obtained from the Tissue-specific Gene Expression and Regulation (TiGER) database. Furthermore, we tested the performance of the tool using two normalization methods, RMA and YuGene. YuGene performed slightly better than RMA. Our tool identified 38,4 % or 37,9 % of the TiGER derived tissue-specific genes using YuGene or RMA, respectively.

scholarly journals Sox17 expression in endocardium precursor cells regulates heart development in mice

2019 ◽  
Author(s):  
Rie Saba ◽  
Keiko Kitajima ◽  
Lucille Rainbow ◽  
Sylvia Engert ◽  
Mami Uemura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Heart Development ◽  
Molecular Mechanisms ◽  
Homeobox Gene ◽  
Cardiac Progenitor Cells ◽  
Cellular Behavior ◽  
Hmg Box ◽  
And Behavior ◽  
Morphology Of The Heart

AbstractThe endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Cardiac progenitor cells (CPCs) that express the homeobox gene Nkx2-5 give rise to the endocardium. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5+ CPCs that express the Sry-type HMG box gene Sox17 specifically differentiate into the endocardium in mouse embryos. Approximately 20% to 30% of Nkx2-5+CPCs transiently express Sox17 from embryonic day (E) 7.5 to E8.5.Although Sox17 is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand, Sox17 expression in the endocardium is required for heart development. Deletion of Sox17 specifically in the mesoderm markedly impaired endocardium development with regard to cell proliferation and behavior. The proliferation of cardiomyocytes, ventricular trabeculation, and myocardium thickening were also impaired in a non–cell-autonomous manner in the Sox17 mutant, resulting in anomalous morphology of the heart, likely as a consequence of down-regulation of NOTCH signaling. Changes in gene expression profile in both the endocardium and myocardium preceded the reduction in NOTCH-related gene expression in the mutant embryos, suggesting that Sox17 expression in the endocardium regulates an unknown signal required for nurturing of the myocardium. Our results thus provide insight into differentiation of the endocardium and its role in heart development.SignificanceThe endocardium is vital for vertebrate heart development; however, the molecular mechanisms regulating fate determination and differentiation remain largely unknown. Here, we show that a part of the earliest cardiac progenitor cells (CPCs) transiently and exclusively express Sry-type HMG box gene Sox17 in the mouse embryo. Sox17-expressing CPCs specifically differentiate to the endocardium. Sox17 biases the fate of CPCs toward the endocardium, and regulates proliferation and cellular behavior cell autonomously. Conversely, Sox17 in the endocardium regulates the myocardium non-cell autonomously. Notably, Sox17 is required for the ventricular trabeculation via the NOTCH signal that is not directly induced but maintained by Sox17. This study, thus, sheds light on endocardium development.

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 Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Hiroshi Kondo ◽  
Keiko Miyoshi ◽  
Shoji Sakiyama ◽  
Akira Tangoku ◽  
Takafumi Noma
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Mapk Pathway ◽  
Alveolar Epithelial Cell ◽  
Marker Gene ◽  
Regulation Of Gene Expression ◽  
Surfactant Protein ◽  
Specific Gene ◽  
Expression Levels ◽  
Alveolar Epithelial

Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated anin vitrosystem to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions,surfactant protein C(SPC), an ATII marker, was upregulated in both H12 and B7.Aquaporin 5(AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited,SPCandthyroid transcription factor-1(TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF),surfactant protein BandTTF-1expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

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.

Regulation of the twist target gene tinman by modular cis-regulatory elements during early mesoderm development

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 4971-4982 ◽  
Author(s):  
Z. Yin ◽  
X.L. Xu ◽  
M. Frasch
Keyword(s):  
Homeobox Gene ◽  
Regulatory Elements ◽  
Bhlh Protein ◽  
Expression Domain ◽  
Enhancer Activity ◽  
Enhancer Element ◽  
Mesoderm Development ◽  
Visceral Mesoderm

The Drosophila tinman homeobox gene has a major role in early mesoderm patterning and determines the formation of visceral mesoderm, heart progenitors, specific somatic muscle precursors and glia-like mesodermal cells. These functions of tinman are reflected in its dynamic pattern of expression, which is characterized by initial widespread expression in the trunk mesoderm, then refinement to a broad dorsal mesodermal domain, and finally restricted expression in heart progenitors. Here we show that each of these phases of expression is driven by a discrete enhancer element, the first being active in the early mesoderm, the second in the dorsal mesoderm and the third in cardioblasts. We provide evidence that the early-active enhancer element is a direct target of twist, a gene encoding a basic helix-loop-helix (bHLH) protein, which is necessary for tinman activation. This 180 bp enhancer includes three E-box sequences which bind Twist protein in vitro and are essential for enhancer activity in vivo. Ectodermal misexpression of twist causes ectopic activation of this enhancer in ectodermal cells, indicating that twist is the only mesoderm-specific activator of early tinman expression. We further show that the 180 bp enhancer also includes negatively acting sequences. Binding of Even-skipped to these sequences appears to reduce twist-dependent activation in a periodic fashion, thus producing a striped tinman pattern in the early mesoderm. In addition, these sequences prevent activation of tinman by twist in a defined portion of the head mesoderm that gives rise to hemocytes. We find that this repression requires the function of buttonhead, a head-patterning gene, and that buttonhead is necessary for normal activation of the hematopoietic differentiation gene serpent in the same area. Together, our results show that tinman is controlled by an array of discrete enhancer elements that are activated successively by differential genetic inputs, as well as by closely linked activator and repressor binding sites within an early-acting enhancer, which restrict twist activity to specific areas within the twist expression domain.

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