Comparative Analysis of Gene Regulatory Network Components in the Auditory Hindbrain of Mice and Chicken

2016 ◽  
Vol 88 (3-4) ◽  
pp. 161-176 ◽  
Author(s):  
Benjamin Pawlik ◽  
Tina Schlüter ◽  
Heiner Hartwich ◽  
Saskia Breuel ◽  
Lennart Heepmann ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Terminal Differentiation ◽  
Neuronal Cell ◽  
Divergent Evolution ◽  
Superior Olivary Complex ◽  
Gene Regulatory

The neurons in the mammalian and avian auditory hindbrain nuclei share a number of significant morphological and physiological properties for fast, secure and precise neurotransmission, such as giant synapses, voltage-gated K+ channels and fast AMPA receptors. Based on the independent evolution of the middle ear in these two vertebrate lineages, on different embryonic origins of the nuclei and on marked differences on the circuit level, these similarities are assumed to reflect convergent evolution. Independent acquisition of similar phenotypes can be produced by divergent evolution of genetic mechanisms or by similar molecular mechanisms. The distinction between these two possibilities requires knowledge of the gene regulatory networks (GRNs) that orchestrate the development of auditory hindbrain structures. We therefore compared the expression pattern of GRN components, both transcription factors (TFs) and noncoding RNA, during terminal differentiation of the auditory hindbrain structures in mouse and chicken when neurons acquire their final morphological and electrophysiological properties. In general, we observed broad expression of these genes in the mouse auditory cochlear nucleus complex and the superior olivary complex at both postnatal day 4 (P4) and at P25, and for the chicken at the equivalent developmental stages, i.e. embryonic day 13 (E13) and at P14-P17. Our data are in agreement with a model based on similar molecular mechanisms underlying terminal differentiation and maintenance of neuronal cell identity in the auditory hindbrain of different vertebrate lineages. This conservation might reflect developmental constraints arising from the tagmatic organization of rhombomeres and the evolutionarily highly conserved GRNs operating in these structures.

scholarly journals Integrative Modelling of Gene Expression and Digital Phenotypes to Describe Senescence in Wheat

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 909
Author(s):  
Anyela Valentina Camargo Rodriguez
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Computational Modelling ◽  
Plant Morphology ◽  
Reproductive Organs ◽  
Biological Trait ◽  
Cereal Grain ◽  
Plant Level

Senescence is the final stage of leaf development and is critical for plants’ fitness as nutrient relocation from leaves to reproductive organs takes place. Although senescence is key in nutrient relocation and yield determination in cereal grain production, there is limited understanding of the genetic and molecular mechanisms that control it in major staple crops such as wheat. Senescence is a highly orchestrated continuum of interacting pathways throughout the lifecycle of a plant. Levels of gene expression, morphogenesis, and phenotypic development all play key roles. Yet, most studies focus on a short window immediately after anthesis. This approach clearly leaves out key components controlling the activation, development, and modulation of the senescence pathway before anthesis, as well as during the later developmental stages, during which grain development continues. Here, a computational multiscale modelling approach integrates multi-omics developmental data to attempt to simulate senescence at the molecular and plant level. To recreate the senescence process in wheat, core principles were borrowed from Arabidopsis Thaliana, a more widely researched plant model. The resulted model describes temporal gene regulatory networks and their effect on plant morphology leading to senescence. Digital phenotypes generated from images using a phenomics platform were used to capture the dynamics of plant development. This work provides the basis for the application of computational modelling to advance understanding of the complex biological trait senescence. This supports the development of a predictive framework enabling its prediction in changing or extreme environmental conditions, with a view to targeted selection for optimal lifecycle duration for improving resilience to climate change.

scholarly journals Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Tarun Karthik Kumar Mamidi ◽  
Jiande Wu ◽  
Chindo Hicks
Keyword(s):  
Signaling Pathways ◽  
Somatic Mutation ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Somatic Mutations ◽  
Multiple Gene ◽  
Gene Regulatory ◽  
Aggressive Tumors ◽  
Prostate Cancers ◽  
Mutation Information

Background. A majority of prostate cancers (PCas) are indolent and cause no harm even without treatment. However, a significant proportion of patients with PCa have aggressive tumors that progress rapidly to metastatic disease and are often lethal. PCa develops through somatic mutagenesis, but emerging evidence suggests that germline genetic variation can markedly contribute to tumorigenesis. However, the causal association between genetic susceptibility and tumorigenesis has not been well characterized. The objective of this study was to map the germline and somatic mutation interaction landscape in indolent and aggressive tumors and to discover signatures of mutated genes associated with each type and distinguishing the two types of PCa. Materials and Methods. We integrated germline mutation information from genome-wide association studies (GWAS) with somatic mutation information from The Cancer Genome Atlas (TCGA) using gene expression data from TCGA on indolent and aggressive PCas as the intermediate phenotypes. Germline and somatic mutated genes associated with each type of PCa were functionally characterized using network and pathway analysis. Results. We discovered gene signatures containing germline and somatic mutations associated with each type and distinguishing the two types of PCa. We discovered multiple gene regulatory networks and signaling pathways enriched with germline and somatic mutations including axon guidance, RAR, WINT, MSP-RON, STAT3, PI3K, TR/RxR, and molecular mechanisms of cancer, NF-kB, prostate cancer, GP6, androgen, and VEGF signaling pathways for indolent PCa and MSP-RON, axon guidance, RAR, adipogenesis, and molecular mechanisms of cancer and NF-kB signaling pathways for aggressive PCa. Conclusion. The investigation revealed germline and somatic mutated genes associated with indolent and aggressive PCas and distinguishing the two types of PCa. The study revealed multiple gene regulatory networks and signaling pathways dysregulated by germline and somatic alterations. Integrative analysis combining germline and somatic mutations is a powerful approach to mapping germline and somatic mutation interaction landscape.

scholarly journals Comparative Transcriptome Analysis Reveals Regulatory Networks during the Maize Ear Shank Elongation Process

2021 ◽  
Vol 22 (13) ◽  
pp. 7029
Author(s):  
Cai-Yun Xiong ◽  
Qing-You Gong ◽  
Hu Pei ◽  
Chang-Jian Liao ◽  
Rui-Chun Yang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Rna Seq ◽  
Short Branch ◽  
Transcriptional Dynamics ◽  
New Varieties ◽  
Elongation Process ◽  
Temporal Expression Pattern ◽  
Maize Ear

In maize, the ear shank is a short branch that connects the ear to the stalk. The length of the ear shank mainly affects the transportation of photosynthetic products to the ear, and also influences the dehydration of the grain by adjusting the tightness of the husks. However, the molecular mechanisms of maize shank elongation have rarely been described. It has been reported that the maize ear shank length is a quantitative trait, but its genetic basis is still unclear. In this study, RNA-seq was performed to explore the transcriptional dynamics and determine the key genes involved in maize shank elongation at four different developmental stages. A total of 8145 differentially expressed genes (DEGs) were identified, including 729 transcription factors (TFs). Some important genes which participate in shank elongation were detected via function annotation and temporal expression pattern analyses, including genes related to signal transduction hormones (auxin, brassinosteroids, gibberellin, etc.), xyloglucan and xyloglucan xyloglucosyl transferase, and transcription factor families. The results provide insights into the genetic architecture of maize ear shanks and developing new varieties with ideal ear shank lengths, enabling adjustments for mechanized harvesting in the future.

scholarly journals Comprehensive Assessment and Network Analysis of the Emerging Genetic Susceptibility Landscape of Prostate Cancer

2013 ◽  
Vol 12 ◽  
pp. CIN.S12128 ◽  
Author(s):  
Chindo Hicks ◽  
Lucio Miele ◽  
Tejaswi Koganti ◽  
Srinivasan Vijayakumar
Keyword(s):  
Prostate Cancer ◽  
Genetic Susceptibility ◽  
Pathway Analysis ◽  
Gene Regulatory Networks ◽  
Genetic Variants ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Comprehensive Assessment ◽  
Increased Risk ◽  
Gene Regulatory

Background Recent advances in high-throughput genotyping have made possible identification of genetic variants associated with increased risk of developing prostate cancer using genome-wide associations studies (GWAS). However, the broader context in which the identified genetic variants operate is poorly understood. Here we present a comprehensive assessment, network, and pathway analysis of the emerging genetic susceptibility landscape of prostate cancer. Methods We created a comprehensive catalog of genetic variants and associated genes by mining published reports and accompanying websites hosting supplementary data on GWAS. We then performed network and pathway analysis using single nucleotide polymorphism (SNP)-containing genes to identify gene regulatory networks and pathways enriched for genetic variants. Results We identified multiple gene networks and pathways enriched for genetic variants including IGF-1, androgen biosynthesis and androgen signaling pathways, and the molecular mechanisms of cancer. The results provide putative functional bridges between GWAS findings and gene regulatory networks and biological pathways.

scholarly journals Chip-seq and gene expression data for the identification of functional sub-pathways: a proof of concept in lung cancer

2020 ◽  
Author(s):  
Xanthoula Atsalaki ◽  
Lefteris Koumakis ◽  
George Potamias ◽  
Manolis Tsiknakis
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Systems Biology ◽  
Gene Expression Data ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Integrative Approach ◽  
Expression Data ◽  
Gene Regulatory

AbstractHigh-throughput technologies, such as chromatin immunoprecipitation (ChIP) with massively parallel sequencing (ChIP-seq) have enabled cost and time efficient generation of immense amount of genome data. The advent of advanced sequencing techniques allowed biologists and bioinformaticians to investigate biological aspects of cell function and understand or reveal unexplored disease etiologies. Systems biology attempts to formulate the molecular mechanisms in mathematical models and one of the most important areas is the gene regulatory networks (GRNs), a collection of DNA segments that somehow interact with each other. GRNs incorporate valuable information about molecular targets that can be corellated to specific phenotype.In our study we highlight the need to develop new explorative tools and approaches for the integration of different types of -omics data such as ChIP-seq and GRNs using pathway analysis methodologies. We present an integrative approach for ChIP-seq and gene expression data on GRNs. Using public microarray expression samples for lung cancer and healthy subjects along with the KEGG human gene regulatory networks, we identified ways to disrupt functional sub-pathways on lung cancer with the aid of CTCF ChIP-seq data, as a proof of concept.We expect that such a systems biology pipeline could assist researchers to identify corellations and causality of transcription factors over functional or disrupted biological sub-pathways.

scholarly journals Evolution of abbreviated development in Heliocidaris erythrogramma dramatically re-wired the highly conserved sea urchin developmental gene regulatory network to decouple signaling center function from ultimate fate

2019 ◽  
Author(s):  
Allison Edgar ◽  
Maria Byrne ◽  
David R. McClay ◽  
Gregory A. Wray
Keyword(s):  
Early Development ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Sea Urchins ◽  
Stabilizing Selection ◽  
Developmental Gene ◽  
Heliocidaris Erythrogramma ◽  
Signaling Center ◽  
Gene Regulatory ◽  
Ultimate Fate

AbstractDevelopmental gene regulatory networks (GRNs) describe the interactions among gene products that drive the differential transcriptional and cell regulatory states that pattern the embryo and specify distinct cell fates. GRNs are often deeply conserved, but whether this is the product of constraint inherent to the network structure or stabilizing selection remains unclear. We have constructed the first formal GRN for early development in Heliocidaris erythrogramma, a species with dramatically accelerated, direct development. This life history switch has important ecological consequences, arose rapidly, and has evolved independently many times in echinoderms, suggesting it is a product of selection. We find that H. erythrogramma exhibits dramatic differences in GRN topology compared with ancestral, indirect-developing sea urchins. In particular, the GRN sub-circuit that directs the early and autonomous commitment of skeletogenic cell precursors in indirect developers appears to be absent in H. erythrogramma, a particularly striking change in relation to both the prior conservation of this sub-circuit and the key role that these cells play ancestrally in early development as the embryonic signaling center. These results show that even highly conserved molecular mechanisms of early development can be substantially reconfigured in a relatively short evolutionary time span, suggesting that selection rather than constraint is responsible for the striking conservation of the GRN among other sea urchins.

scholarly journals Characterization of eyes, photoreceptors and opsins in developmental stages of the chaetognath Spadella cephaloptera

2019 ◽  
Author(s):  
Tim Wollesen ◽  
Sonia Victoria Rodríguez Monje ◽  
Adam Phillip Oel ◽  
Detlev Arendt
Keyword(s):  
Regulatory Networks ◽  
Developmental Stages ◽  
Photoreceptor Cells ◽  
Phylogenetic Position ◽  
Developmental Studies ◽  
Head Region ◽  
Platynereis Dumerilii ◽  
Spadella Cephaloptera ◽  
Gene Regulatory

AbstractThe phylogenetic position of chaetognaths has been debated for decades, however recently they have been grouped into the Gnathifera, sister taxon to the Lophotrochozoa. Chaetognaths possess photoreceptor cells that are anatomically unique and arranged remarkably different in the eyes of the various species. Studies investigating eye development and underlying gene regulatory networks are so far missing.In order to gain insights into the development and the molecular toolkit of chaetognath photoreceptors and eyes a new transcriptome of the epibenthic species Spadella cephaloptera was searched for opsins. Our screen revealed single-copies of xenopsin and peropsin and gene expression analyses demonstrated that only xenopsin is expressed in photoreceptor cells of the developing lateral eyes. Adults likewise exhibit two xenopsin+ photoreceptor cells in each of their lateral eyes. Beyond that, a single cryptochrome gene was uncovered and found co-expressed with xenopsin in some photoreceptor cells of the lateral developing eye. In addition, it is co-expressed with peropsin in the cerebral ganglia, a condition reminiscent of a non-visual photoreceptive zone in the apical nervous system of the annelid Platynereis dumerilii that performs circadian entrainment and melatonin release. Cryptochrome expression was also detected in cells of the corona ciliata, a circular organ in the posterior dorsal head region that has been attributed several functions arguing for an involvement of this organ in circadian entrainment. Our study demonstrates the importance to investigate representatives of the Gnathifera, a clade that has been neglected with respect to developmental studies and that might contribute to unravel the evolution of spiralian and bilaterian body plans.

scholarly journals Single cell and single nucleus RNA-Seq reveal cellular heterogeneity and homeostatic regulatory networks in adult mouse stria vascularis

2019 ◽  
Author(s):  
Soumya Korrapati ◽  
Ian Taukulis ◽  
Rafal Olszewski ◽  
Madeline Pyle ◽  
Shoujun Gu ◽  
...  
Keyword(s):  
Single Cell ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Stria Vascularis ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Genetic Mechanisms ◽  
Single Nucleus ◽  
Gene Regulatory

AbstractThe stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell mechanotransduction and hearing. While channels belonging to SV cell types are known to play crucial roles in EP generation, relatively little is known about gene regulatory networks that underlie the ability of the SV to generate and maintain the EP. Using single cell and single nucleus RNA-sequencing, we identify and validate known and rare cell populations in the SV. Furthermore, we establish a basis for understanding molecular mechanisms underlying SV function by identifying potential gene regulatory networks as well as druggable gene targets. Finally, we associate known deafness genes with adult SV cell types. This work establishes a basis for dissecting the genetic mechanisms underlying the role of the SV in hearing and will serve as a basis for designing therapeutic approaches to hearing loss related to SV dysfunction.

scholarly journals Integrating transcriptome and metabolome reveals molecular networks involved in genetic and environmental variation in tobacco

DNA Research ◽  
2020 ◽  
Vol 27 (2) ◽  
Author(s):  
Pingping Liu ◽  
Jie Luo ◽  
Qingxia Zheng ◽  
Qiansi Chen ◽  
Niu Zhai ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
De Novo ◽  
Developmental Process ◽  
Pearson Correlation ◽  
Molecular Networks ◽  
Environmental Perturbations ◽  
Carotenoid Metabolism ◽  
Gene Modules

Abstract Tobacco (Nicotiana tabacum) is one of the most widely cultivated commercial non-food crops with significant social and economic impacts. Here we profiled transcriptome and metabolome from 54 tobacco samples (2–3 replicates; n = 151 in total) collected from three varieties (i.e. genetic factor), three locations (i.e. environmental factor), and six developmental stages (i.e. developmental process). We identified 3,405 differentially expressed (DE) genes (DEGs) and 371 DE metabolites, respectively. We used quantitative real-time PCR to validate 20 DEGs, and confirmed 18/20 (90%) DEGs between three locations and 16/20 (80%) with the same trend across developmental stages. We then constructed nine co-expression gene modules and four co-expression metabolite modules , and defined seven de novo regulatory networks, including nicotine- and carotenoid-related regulatory networks. A novel two-way Pearson correlation approach was further proposed to integrate co-expression gene and metabolite modules to identify joint gene–metabolite relations. Finally, we further integrated DE and network results to prioritize genes by its functional importance and identified a top-ranked novel gene, LOC107773232, as a potential regulator involved in the carotenoid metabolism pathway. Thus, the results and systems-biology approaches provide a new avenue to understand the molecular mechanisms underlying complex genetic and environmental perturbations in tobacco.

The Genetics of Evolutionary Novelties

2014 ◽  
Author(s):  
Günter P. Wagner
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Regulatory Elements ◽  
Complex Problem ◽  
Micro Rnas ◽  
Sex Comb ◽  
Gene Regulatory ◽  
Transcription Factor Proteins ◽  
Evolutionary Novelties

This chapter examines the molecular genetics of evolutionary novelties. In particular, it investigates which molecular mechanisms might be involved in the origination of novel gene regulatory networks (and, thus, character identity networks) and what these mechanisms imply for the origin of novel characters. The chapter begins with a discussion of the complex problem of the evolution of transcriptional regulation by focusing on the evolution of cis-regulatory elements (CREs) and the evolution of transcription factor proteins. It then asks whether novel pigment spots, such as the Drosophila wing spots, are novelties. It also explores an evolutionary novelty known as sex comb and the role of transposable elements in the origin of novel CREs. Finally, it considers the role of gene duplications, the evolution of micro-RNAs (miRNAs), and the possibility of a mechanistic difference between adaptation and innovation.

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