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Gene Network (gene + network)
Selected AbstractsGene networks controlling early cerebral cortex arealizationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Antonello Mallamaci Abstract Early thalamus-independent steps in the process of cortical arealization take place on the basis of information intrinsic to the cortical primordium, as proposed by Rakic in his classical protomap hypothesis [Rakic, P. (1988)Science, 241, 170,176]. These steps depend on a dense network of molecular interactions, involving genes encoding for diffusible ligands which are released around the borders of the cortical field, and transcription factor genes which are expressed in graded ways throughout this field. In recent years, several labs worldwide have put considerable effort into identifying members of this network and disentangling its topology. In this respect, a considerable amount of knowledge has accumulated and a first, provisional description of the network can be delineated. The aim of this review is to provide an organic synthesis of our current knowledge of molecular genetics of early cortical arealization, i.e. to summarise the mechanisms by which secreted ligands and graded transcription factor genes elaborate positional information and trigger the activation of distinctive area-specific morphogenetic programs. [source] Gene networks and liar paradoxesBIOESSAYS, Issue 10 2009Mark Isalan Abstract Network motifs are small patterns of connections, found over-represented in gene regulatory networks. An example is the negative feedback loop (e.g. factor A represses itself). This opposes its own state so that when ,on' it tends towards ,off' , and vice versa. Here, we argue that such self-opposition, if considered dimensionlessly, is analogous to the liar paradox: ,This statement is false'. When ,true' it implies ,false' , and vice versa. Such logical constructs have provided philosophical consternation for over 2000,years. Extending the analogy, other network topologies give strikingly varying outputs over different dimensions. For example, the motif ,A activates B and A. B inhibits A' can give switches or oscillators with time only, or can lead to Turing-type patterns with both space and time (spots, stripes or waves). It is argued here that the dimensionless form reduces to a variant of ,The following statement is true. The preceding statement is false'. Thus, merely having a static topological description of a gene network can lead to a liar paradox. Network diagrams are only snapshots of dynamic biological processes and apparent paradoxes can reveal important biological mechanisms that are far from paradoxical when considered explicitly in time and space. [source] Evolutionary conservation and divergence of the segmentation process in arthropodsDEVELOPMENTAL DYNAMICS, Issue 6 2007Wim G. M. Damen Abstract A fundamental characteristic of the arthropod body plan is its organization in metameric units along the anterior,posterior axis. The segmental organization is laid down during early embryogenesis. Our view on arthropod segmentation is still strongly influenced by the huge amount of data available from the fruit fly Drosophila melanogaster (the Drosophila paradigm). However, the simultaneous formation of the segments in Drosophila is a derived mode of segmentation. Successive terminal addition of segments from a posteriorly localized presegmental zone is the ancestral mode of arthropod segmentation. This review focuses on the evolutionary conservation and divergence of the genetic mechanisms of segmentation within arthropods. The more downstream levels of the segmentation gene network (e.g., segment polarity genes) appear to be more conserved than the more upstream levels (gap genes, Notch/Delta signaling). Surprisingly, the basally branched arthropod groups also show similarities to mechanisms used in vertebrate somitogenesis. Furthermore, it has become clear that the activation of pair rule gene orthologs is a key step in the segmentation of all arthropods. Important findings of conserved and diverged aspects of segmentation from the last few years now allow us to draw an evolutionary scenario on how the mechanisms of segmentation could have evolved and led to the present mechanisms seen in various insect groups including dipterans like Drosophila. Developmental Dynamics 236:1379,1391, 2007. © 2007 Wiley-Liss, Inc. [source] The dynamics of developmental system drift in the gene network underlying wing polyphenism in ants: a mathematical modelEVOLUTION AND DEVELOPMENT, Issue 3 2008Marcos Nahmad SUMMARY Understanding the complex interaction between genotype and phenotype is a major challenge of Evolutionary Developmental Biology. One important facet of this complex interaction has been called "Developmental System Drift" (DSD). DSD occurs when a similar phenotype, which is homologous across a group of related species, is produced by different genes or gene expression patterns in each of these related species. We constructed a mathematical model to explore the developmental and evolutionary dynamics of DSD in the gene network underlying wing polyphenism in ants. Wing polyphenism in ants is the ability of an embryo to develop into a winged queen or a wingless worker in response to an environmental cue. Although wing polyphenism is homologous across all ants, the gene network that underlies wing polyphenism has evolved. In winged ant castes, our simulations reproduced the conserved gene expression patterns observed in the network that controls wing development in holometabolous insects. In wingless ant castes, we simulated the suppression of wings by interrupting (up- or downregulating) the expression of genes in the network. Our simulations uncovered the existence of four groups of genes that have similar effects on target gene expression and growth. Although each group is comprised of genes occupying different positions in the network, their interruption produces vestigial discs that are similar in size and shape. The implications of our results for understanding the origin, evolution, and dissociation of the gene network underlying wing polyphenism in ants are discussed. [source] RhoA, encoding a Rho GTPase, is associated with smoking initiationGENES, BRAIN AND BEHAVIOR, Issue 8 2007X. Chen We used microarray analysis of acute nicotine responses in mouse brain to choose rationale candidates for human association studies on tobacco smoking and nicotine dependence (ND). Microarray studies on the time,course of acute response to nicotine in mouse brain identified 95 genes regulated in ventral tegmental area. Among these, 30 genes were part of a gene network, with functions relevant to neural plasticity. On this basis and their known roles in drug abuse or synaptic plasticity, we chose the genes RhoA and Ywhag as candidates for human association studies. A synteny search identified human orthologs and we investigated their role in tobacco smoking and ND in a human case,control association study. We genotyped five and three single nucleotide polymorphisms from the RhoA and Ywhag genes, respectively. Both single marker and haplotype analyses were negative for the Ywhag gene. For the RhoA gene, rs2878298 showed highly significant genotypic association with both smoking initiation (SI) and ND (P = 0.00005 for SI and P = 0.0007 for ND). In the allelic analyses, rs2878298 was only significant for SI. In the multimarker haplotype analyses, significant association with SI was found for the RhoA gene (empirical global P values ranged from 9 × 10,5 to 10,5). In all multimarker combinations analyzed, with or without inclusion of the single most significant marker rs2878298, identical risk and protective haplotypes were identified. Our results indicated that the RhoA gene is likely involved in initiation of tobacco smoking and ND. Replication and future model system studies will be needed to validate the role of RhoA gene in SI and ND. [source] Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C,HEPATOLOGY, Issue 5 2006Masao Honda The clinical manifestations of chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH-B or CH-C; however, the signaling pathways underlying each condition have yet to be clarified. Using a newly constructed cDNA microarray consisting of 9614 clones selected from 256,550 tags of hepatic serial analysis of gene expression (SAGE) libraries, we compared the gene expression profiles of liver tissue from 24 CH-B patients with those of 23 CH-C patients. Laser capture microdissection was used to isolate hepatocytes from liver lobules and infiltrating lymphoid cells from the portal area, from 16 patients, for gene expression analysis. Furthermore, the comprehensive gene network was analyzed using SAGE libraries of CH-B and CH-C. Supervised and nonsupervised learning methods revealed that gene expression was correlated more with the infecting virus than any other clinical parameters such as histological stage and disease activity. Pro-apoptotic and DNA repair responses were predominant in CH-B with p53 and 14-3-3 interacting genes having an important role. In contrast, inflammatory and anti-apoptotic phenotypes were predominant in CH-C. These differences would evoke different oncogenic factors in CH-B and CH-C. In conclusion, we describe the different signaling pathways induced in the livers of patients with CH-B or CH-C. The results might be useful in guiding therapeutic strategies to prevent the development of hepatocellular carcinoma in cases of CH-B and CH-C. (HEPATOLOGY 2006;44:1122,1138.) [source] AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010Vojislav Jovanovic Abstract Tolerance is the so-called "Holy Grail" of transplantation but achieving this state is proving a major challenge, particularly in the clinical settings. This tolerance state can be induced in rodent models using a variety of maneuvers. This phenomenon is classically characterized by donor specificity (recipients accept a secondary donor-specific allograft but reject third-party allograft) as well as by the absence of chronic rejection lesion. We previously showed that administration and anti-donor anti-class II serum on the day of transplantation induce tolerance to a kidney allograft in the LEW-1W to LEW-1A strain combination. In this study, we used DNA microarrays to compare gene patterns involved in anti-donor anti-class II tolerated or untreated syngeneic kidney transplants in this strain combination. Statistical and non-statistical analyses were combined with ab initio analysis, using the recently developed leader gene approach, to shed new light on this phenomenon. Theoretical and experimental results suggest that tolerance and rejection outcome may be in large part determined by low expression variations of some genes, which can form a core gene network around specific genes such as Rac1, NFKB1, RelA, AKT1, IKBKB, BCL2, BCLX, and CHUK. Through this model, we showed that AKT1 gene, WNT pathway and NO synthesis are strictly connected to each other and may play an important role in kidney tolerance and rejection processes, with AKT1 gene being the center of this complex network of interactions. J. Cell. Biochem. 111: 709,719, 2010. © 2010 Wiley-Liss, Inc. [source] Conservation and diversification of the symmetry developmental program among close relatives of snapdragon with divergent floral morphologiesNEW PHYTOLOGIST, Issue 3 2009Jill C. Preston Summary ,,Multiple evolutionary shifts in floral symmetry and stamen number have occurred in the snapdragon (Antirrhinum majus) family Veronicaceae. In Mohavea, Veronica and Gratiola there have been independent evolutionary reductions in stamen number and modifications to corolla shape. It is hypothesized that changes in the regulation of homologs of snapdragon dorsal flower identity genes CYCLOIDEA (CYC) and RADIALIS (RAD) underlie these floral transitions. ,,CYC -like and RAD -like genes from Veronica montana and Gratiola officinalis were cloned and sequenced, compared with homologs from other Veronicaceae species using phylogenetic analysis, and their expression was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization. ,,VmCYC1, GoCYC1, GoCYC2 and RAD -like genes are expressed exclusively in the dorsal region of floral meristems and developing flowers. Their expression patterns do not correlate with patterns of stamen arrest. VmCYC2 and GoCYC3 are expressed in both vegetative and floral tissues, with VmCYC2 being most abundant in all regions of the floral meristem and all petals. ,,These results support conservation of the floral symmetry gene network for Veronicaceae RAD -like and some CYC -like paralogs, suggest regulatory evolution of other CYC -like genes following gene duplication and implicate different genetic mechanisms underlying dorsal versus ventral stamen abortion within Veronica and Gratiola. [source] The H19 locus: Role of an imprinted non-coding RNA in growth and developmentBIOESSAYS, Issue 6 2010Anne Gabory Abstract The H19 gene produces a non-coding RNA, which is abundantly expressed during embryonic development and down-regulated after birth. Although this gene was discovered over 20 years ago, its function has remained unclear. Only recently a role was identified for the non-coding RNA and/or its microRNA partner, first as a tumour suppressor gene in mice, then as a trans-regulator of a group of co-expressed genes belonging to the imprinted gene network that is likely to control foetal and early postnatal growth in mice. The mechanisms underlying this transcriptional or post-transcriptional regulation remain to be discovered, perhaps by identifying the protein partners of the full-length H19 RNA or the targets of the microRNA. This first in vivo evidence of a functional role for the H19 locus provides new insights into how genomic imprinting helps to control embryonic growth. [source] Gene networks and liar paradoxesBIOESSAYS, Issue 10 2009Mark Isalan Abstract Network motifs are small patterns of connections, found over-represented in gene regulatory networks. An example is the negative feedback loop (e.g. factor A represses itself). This opposes its own state so that when ,on' it tends towards ,off' , and vice versa. Here, we argue that such self-opposition, if considered dimensionlessly, is analogous to the liar paradox: ,This statement is false'. When ,true' it implies ,false' , and vice versa. Such logical constructs have provided philosophical consternation for over 2000,years. Extending the analogy, other network topologies give strikingly varying outputs over different dimensions. For example, the motif ,A activates B and A. B inhibits A' can give switches or oscillators with time only, or can lead to Turing-type patterns with both space and time (spots, stripes or waves). It is argued here that the dimensionless form reduces to a variant of ,The following statement is true. The preceding statement is false'. Thus, merely having a static topological description of a gene network can lead to a liar paradox. Network diagrams are only snapshots of dynamic biological processes and apparent paradoxes can reveal important biological mechanisms that are far from paradoxical when considered explicitly in time and space. [source] Incorporating Predictor Network in Penalized Regression with Application to Microarray DataBIOMETRICS, Issue 2 2010Wei Pan Summary We consider penalized linear regression, especially for "large,p, small,n" problems, for which the relationships among predictors are described a priori by a network. A class of motivating examples includes modeling a phenotype through gene expression profiles while accounting for coordinated functioning of genes in the form of biological pathways or networks. To incorporate the prior knowledge of the similar effect sizes of neighboring predictors in a network, we propose a grouped penalty based on the,L, -norm that smoothes the regression coefficients of the predictors over the network. The main feature of the proposed method is its ability to automatically realize grouped variable selection and exploit grouping effects. We also discuss effects of the choices of the , and some weights inside the,L, -norm. Simulation studies demonstrate the superior finite-sample performance of the proposed method as compared to Lasso, elastic net, and a recently proposed network-based method. The new method performs best in variable selection across all simulation set-ups considered. For illustration, the method is applied to a microarray dataset to predict survival times for some glioblastoma patients using a gene expression dataset and a gene network compiled from some Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. [source] Bayesian Inference for Stochastic Kinetic Models Using a Diffusion ApproximationBIOMETRICS, Issue 3 2005A. Golightly Summary This article is concerned with the Bayesian estimation of stochastic rate constants in the context of dynamic models of intracellular processes. The underlying discrete stochastic kinetic model is replaced by a diffusion approximation (or stochastic differential equation approach) where a white noise term models stochastic behavior and the model is identified using equispaced time course data. The estimation framework involves the introduction of m, 1 latent data points between every pair of observations. MCMC methods are then used to sample the posterior distribution of the latent process and the model parameters. The methodology is applied to the estimation of parameters in a prokaryotic autoregulatory gene network. [source] Reactive oxygen signaling and abiotic stressPHYSIOLOGIA PLANTARUM, Issue 3 2008Gad Miller Reactive oxygen species (ROS) play a dual role in plant biology acting on the one hand as important signal transduction molecules and on the other as toxic by-products of aerobic metabolism that accumulate in cells during different stress conditions. Because of their toxicity as well as their important signaling role, the level of ROS in cells is tightly controlled by a vast network of genes termed the ,ROS gene network'. Using mutants deficient in key ROS-scavenging enzymes, we have defined a signaling pathway that is activated in cells in response to ROS accumulation. Interestingly, many of the key players in this pathway, including different zinc finger proteins and WRKY transcription factors, are also central regulators of abiotic stress responses involved in temperature, salinity and osmotic stresses. Here, we describe our recent findings and discuss how ROS integrate different signals originating from different cellular compartments during abiotic stress. [source] Hormone response to bidirectional selection on social behaviorEVOLUTION AND DEVELOPMENT, Issue 5 2010Gro V. Amdam SUMMARY Behavior is a quantitative trait determined by multiple genes. Some of these genes may have effects from early development and onward by influencing hormonal systems that are active during different life-stages leading to complex associations, or suites, of traits. Honey bees (Apis mellifera) have been used extensively in experiments on the genetic and hormonal control of complex social behavior, but the relationships between their early developmental processes and adult behavioral variation are not well understood. Bidirectional selective breeding on social food-storage behavior produced two honey bee strains, each with several sublines, that differ in an associated suite of anatomical, physiological, and behavioral traits found in unselected wild type bees. Using these genotypes, we document strain-specific changes during larval, pupal, and early adult life-stages for the central insect hormones juvenile hormone (JH) and ecdysteroids. Strain differences correlate with variation in female reproductive anatomy (ovary size), which can be influenced by JH during development, and with secretion rates of ecdysteroid from the ovaries of adults. Ovary size was previously assigned to the suite of traits of honey bee food-storage behavior. Our findings support that bidirectional selection on honey bee social behavior acted on pleiotropic gene networks. These networks may bias a bee's adult phenotype by endocrine effects on early developmental processes that regulate variation in reproductive traits. [source] Upregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis,HEPATOLOGY, Issue 5 2006Pierre J. Zindy The molecular mechanisms underlying the progression of cirrhosis toward hepatocellular carcinoma were investigated by a combination of DNA microarray analysis and literature data mining. By using a microarray screening of suppression subtractive hybridization cDNA libraries, we first analyzed genes differentially expressed in tumor and nontumor livers with cirrhosis from 15 patients with hepatocellular carcinomas. Seventy-four genes were similarly recovered in tumor (57.8% of differentially expressed genes) and adjacent nontumor tissues (64% of differentially expressed genes) compared with histologically normal livers. Gene ontology analyses revealed that downregulated genes (n = 35) were mostly associated with hepatic functions. Upregulated genes (n = 39) included both known genes associated with extracellular matrix remodeling, cell communication, metabolism, and post-transcriptional regulation gene (e.g., ZFP36L1), as well as the tumor suppressor gene menin (multiple endocrine neoplasia type 1; MEN1). MEN1 was further identified as an important node of a regulatory network graph that integrated array data with array-independent literature mining. Upregulation of MEN1 in tumor was confirmed in an independent set of samples and associated with tumor size (P = .016). In the underlying liver with cirrhosis, increased steady-state MEN1 mRNA levels were correlated with those of collagen ,2(I) mRNA (P < .01). In addition, MEN1 expression was associated with hepatic stellate cell activation during fibrogenesis and involved in transforming growth factor beta (TGF-,),dependent collagen ,2(I) regulation. In conclusion, menin is a key regulator of gene networks that are activated in fibrogenesis associated with hepatocellular carcinoma through the modulation of TGF-, response. (HEPATOLOGY 2006;44:1296,1307.) [source] Upward mobility and alternative lifestyles: a report from the 10th biennial meeting on Bacterial Locomotion and Signal TransductionMOLECULAR MICROBIOLOGY, Issue 1 2009Birgit E. Scharf Summary This past January, in Cuernavaca Mexico, a conglomerate of scientists met to discuss the contemporary view of Bacterial Locomotion and Signal Transduction (BLAST). The BLAST meetings represent a field that has its roots in chemotaxis and the flagellum-based motility but now encompass all types of cellular movement and signalling. The topics varied from the interactions between molecules to the interactions between species. We heard about 3D reconstructions of transmembrane chemoreceptors within cells, new biophysical methods for understanding cellular engines, intricate phosphorelays, elaborate gene networks, new messenger molecules and emerging behaviours within complex populations of cells. At BLAST X we gained an appreciation for the lifestyle choices bacteria make, how they get to where they are going and the molecular mechanisms that underlie their decisions. Herein we review the highlights of the meeting. [source] Pharmacologic transgene control systems for gene therapyTHE JOURNAL OF GENE MEDICINE, Issue 5 2006Wilfried Weber Abstract Pharmacologic transgene-expression dosing is considered essential for future gene therapy scenarios. Genetic interventions require precise transcription or translation fine-tuning of therapeutic transgenes to enable their titration into the therapeutic window, to adapt them to daily changing dosing regimes of the patient, to integrate them seamlessly into the patient's transcriptome orchestra, and to terminate their expression after successful therapy. In recent years, decisive progress has been achieved in designing high-precision trigger-inducible mammalian transgene control modalities responsive to clinically licensed and inert heterologous molecules or to endogenous physiologic signals. Availability of a portfolio of compatible transcription control systems has enabled assembly of higher-order control circuitries providing simultaneous or independent control of several transgenes and the design of (semi-)synthetic gene networks, which emulate digital expression switches, regulatory transcription cascades, epigenetic expression imprinting, and cellular transcription memories. This review provides an overview of cutting-edge developments in transgene control systems, of the design of synthetic gene networks, and of the delivery of such systems for the prototype treatment of prominent human disease phenotypes. Copyright © 2006 John Wiley & Sons, Ltd. [source] Seed after-ripening is a discrete developmental pathway associated with specific gene networks in ArabidopsisTHE PLANT JOURNAL, Issue 2 2008Esther Carrera Summary After-ripening (AR) is a time and environment regulated process occurring in the dry seed, which determines the germination potential of seeds. Both metabolism and perception of the phytohormone abscisic acid (ABA) are important in the initiation and maintenance of dormancy. However, molecular mechanisms that regulate the capacity for dormancy or germination through AR are unknown. To understand the relationship between ABA and AR, we analysed genome expression in Arabidopsis thaliana mutants defective in seed ABA synthesis (aba1-1) or perception (abi1-1). Even though imbibed mutant seeds showed no dormancy, they exhibited changes in global gene expression resulting from dry AR that were comparable with changes occurring in wild-type (WT) seeds. Core gene sets were identified that were positively or negatively regulated by dry seed storage. Each set included a gene encoding repression or activation of ABA function (LPP2 and ABA1, respectively), thereby suggesting a mechanism through which dry AR may modulate subsequent germination potential in WT seeds. Application of exogenous ABA to after-ripened WT seeds did not reimpose characteristics of freshly harvested seeds on imbibed seed gene expression patterns. It was shown that secondary dormancy states reinstate AR status-specific gene expression patterns. A model is presented that separates the action of ABA in seed dormancy from AR and dry storage regulated gene expression. These results have major implications for the study of genetic mechanisms altered in seeds as a result of crop domestication into agriculture, and for seed behaviour during dormancy cycling in natural ecosystems. [source] Differential Expression and Network Inferences through Functional Data ModelingBIOMETRICS, Issue 3 2009Donatello Telesca Summary Time course microarray data consist of mRNA expression from a common set of genes collected at different time points. Such data are thought to reflect underlying biological processes developing over time. In this article, we propose a model that allows us to examine differential expression and gene network relationships using time course microarray data. We model each gene-expression profile as a random functional transformation of the scale, amplitude, and phase of a common curve. Inferences about the gene-specific amplitude parameters allow us to examine differential gene expression. Inferences about measures of functional similarity based on estimated time-transformation functions allow us to examine gene networks while accounting for features of the gene-expression profiles. We discuss applications to simulated data as well as to microarray data on prostate cancer progression. [source] | ||||||||||||||||||||||