Ultrabithorax Is a Micromanager of Hindwing Identity in Butterflies and Moths

The forewings and hindwings of butterflies and moths (Lepidoptera) are differentiated from each other, with segment-specific morphologies and color patterns that mediate a wide range of functions in flight, signaling, and protection. The Hox gene Ultrabithorax (Ubx) is a master selector gene that differentiates metathoracic from mesothoracic identities across winged insects, and previous work has shown this role extends to at least some of the color patterns from the butterfly hindwing. Here we used CRISPR targeted mutagenesis to generate Ubx loss-of-function somatic mutations in two nymphalid butterflies (Junonia coenia, Vanessa cardui) and a pyralid moth (Plodia interpunctella). The resulting mosaic clones yielded hindwing-to-forewing transformations, showing Ubx is necessary for specifying many aspects of hindwing-specific identities, including scale morphologies, color patterns, and wing venation and structure. These homeotic phenotypes showed cell-autonomous, sharp transitions between mutant and non-mutant scales, except for clones that encroached into the border ocelli (eyespots) and resulted in composite and non-autonomous effects on eyespot ring determination. In the pyralid moth, homeotic clones converted the folding and depigmented hindwing into rigid and pigmented composites, affected the wing-coupling frenulum, and induced ectopic scent-scales in male androconia. These data confirm Ubx is a master selector of lepidopteran hindwing identity and suggest it acts on many gene regulatory networks involved in wing development and patterning.

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NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets

eLife ◽

10.7554/elife.06942 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 26

Author(s):

Romaric Bouveret ◽

Ashley J Waardenberg ◽

Nicole Schonrock ◽

Mirana Ramialison ◽

Tram Doan ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Regulatory Networks ◽

Congenital Heart ◽

Target Genes ◽

Loss Of Function ◽

Wild Type ◽

Interaction Domain ◽

Ets Proteins ◽

Gene Regulatory

We take a functional genomics approach to congenital heart disease mechanism. We used DamID to establish a robust set of target genes for NKX2-5 wild type and disease associated NKX2-5 mutations to model loss-of-function in gene regulatory networks. NKX2-5 mutants, including those with a crippled homeodomain, bound hundreds of targets including NKX2-5 wild type targets and a unique set of "off-targets", and retained partial functionality. NKXΔHD, which lacks the homeodomain completely, could heterodimerize with NKX2-5 wild type and its cofactors, including E26 transformation-specific (ETS) family members, through a tyrosine-rich homophilic interaction domain (YRD). Off-targets of NKX2-5 mutants, but not those of an NKX2-5 YRD mutant, showed overrepresentation of ETS binding sites and were occupied by ETS proteins, as determined by DamID. Analysis of kernel transcription factor and ETS targets show that ETS proteins are highly embedded within the cardiac gene regulatory network. Our study reveals binding and activities of NKX2-5 mutations on WT target and off-targets, guided by interactions with their normal cardiac and general cofactors, and suggest a novel type of gain-of-function in congenital heart disease.

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Evolutionary selection for protein aggregation

Biochemical Society Transactions ◽

10.1042/bst20120160 ◽

2012 ◽

Vol 40 (5) ◽

pp. 1032-1037 ◽

Cited By ~ 25

Author(s):

Natalia Sanchez de Groot ◽

Marc Torrent ◽

Anna Villar-Piqué ◽

Benjamin Lang ◽

Salvador Ventura ◽

...

Keyword(s):

Protein Aggregation ◽

Protein Interactions ◽

Current Knowledge ◽

Protein Aggregates ◽

Cellular Systems ◽

Aggregation Process ◽

Loss Of Function ◽

Protein Protein Interactions ◽

Wide Range ◽

Range Of Functions

Protein aggregation is being found to be associated with an increasing number of human diseases. Aggregation can lead to a loss of function (lack of active protein) or to a toxic gain of function (cytotoxicity associated with protein aggregates). Although potentially harmful, protein sequences predisposed to aggregation seem to be ubiquitous in all kingdoms of life, which suggests an evolutionary advantage to having such segments in polypeptide sequences. In fact, aggregation-prone segments are essential for protein folding and for mediating certain protein–protein interactions. Moreover, cells use protein aggregates for a wide range of functions. Against this background, life has adapted to tolerate the presence of potentially dangerous aggregation-prone sequences by constraining and counteracting the aggregation process. In the present review, we summarize the current knowledge of the advantages associated with aggregation-prone stretches in proteomes and the strategies that cellular systems have developed to control the aggregation process.

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Input dose differentiation by NF-κB

10.1101/752394 ◽

2019 ◽

Cited By ~ 1

Author(s):

Minjun Son ◽

Andrew Wang ◽

Hsiung-Lin Tu ◽

Marie O Metzig ◽

Parthiv Patel ◽

...

Keyword(s):

Regulatory Networks ◽

Short Term Memory ◽

Single Cells ◽

Absolute Difference ◽

Transcriptional Responses ◽

Wide Range ◽

Negative Feedbacks ◽

Gene Regulatory ◽

Complex Signaling ◽

Simple Network

AbstractCells receive a wide range of dynamic signaling inputs during immune regulation, but how gene regulatory networks measure and interpret such dynamic inputs is not understood. Here, we used microfluidic live-cell analysis and mathematical modeling to study how NF-κB pathway in single-cells responds to time-varying immune inputs such as increasing, decreasing or fluctuating cytokine signals. Surprisingly, we found that NF-κB acts as a differentiator, responding strictly to the absolute difference in cytokine concentration, and not to the concentration itself. Our analyses revealed that negative feedbacks by the regulatory proteins A20 and IκBα enable dose differentiation by providing short-term memory of prior cytokine level and continuously resetting kinase cycling and receptor levels. Investigation of NF-κB target gene expression showed that cells create unique transcriptional responses under different dynamic cytokine profiles. Our results demonstrate how cells use simple network motifs and transcription factor dynamics to efficiently extract information from complex signaling environments.

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Neuron subtype-specific effector gene expression in the Motor Ganglion of Ciona

10.1101/641233 ◽

2019 ◽

Cited By ~ 1

Author(s):

Susanne Gibboney ◽

Kwantae Kim ◽

Christopher J. Johnson ◽

Jameson Orvis ◽

Paula Martínez-Feduchi ◽

...

Keyword(s):

Gene Expression ◽

Regulatory Networks ◽

Gene Expression Analysis ◽

Transcriptome Profiling ◽

Matrix Proteins ◽

Wide Range ◽

Specific Effector ◽

The Central Nervous System ◽

Differential Gene ◽

Gene Regulatory

AbstractThe central nervous system of the Ciona larva contains only 177 neurons. The precise regulation of neuron subtype-specific morphogenesis and differentiation observed in during the formation of this minimal connectome offers a unique opportunity to dissect gene regulatory networks underlying chordate neurodevelopment. Here we compare the transcriptomes of two very distinct neuron types in the hindbrain/spinal cord homolog of Ciona, the Motor Ganglion (MG): the Descending decussating neuron (ddN, proposed homolog of Mauthner Cells in vertebrates) and the MG Interneuron 2 (MGIN2). Both types are invariantly represented by a single bilaterally symmetric left/right pair of cells in every larva. Supernumerary ddNs and MGIN2s were generated in synchronized embryos and isolated by fluorescence-activated cell sorting for transcriptome profiling. Differential gene expression analysis revealed ddN- and MGIN2-specific enrichment of a wide range of genes, including many encoding potential “effectors” of subtype-specific morphological and functional traits. More specifically, we identified the upregulation of centrosome-associated, microtubule-stabilizing/bundling proteins and extracellular matrix proteins and axon guidance cues as part of a single intrinsic regulatory program that might underlie the unique polarization of the ddNs, the only descending MG neurons that cross the midline.

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Prioritizing candidate disease-related long non-coding RNAs by walking on the heterogeneous lncRNA and disease network

Molecular BioSystems ◽

10.1039/c4mb00511b ◽

2015 ◽

Vol 11 (3) ◽

pp. 760-769 ◽

Cited By ~ 109

Author(s):

Meng Zhou ◽

Xiaojun Wang ◽

Jiawei Li ◽

Dapeng Hao ◽

Zhenzhen Wang ◽

...

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

Biological Processes ◽

Disease Network ◽

Wide Range ◽

Gene Regulatory ◽

Non Coding Rnas

Accumulated evidence has shown that long non-coding RNAs (lncRNA) act as a widespread layer in gene regulatory networks and are involved in a wide range of biological processes.

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On the Study of Reverse Degree-Based Topological Properties for the Third Type of p th Chain Hex-Derived Network

Journal of Mathematics ◽

10.1155/2021/4540276 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Ali N. A. Koam ◽

Ali Ahmad ◽

Ashfaq Ahmed Qummer

Keyword(s):

Computer Science ◽

Regulatory Networks ◽

Metabolic Networks ◽

Environmental Chemistry ◽

Global Network ◽

Network Characteristics ◽

The Third ◽

Degree Of A Vertex ◽

Wide Range ◽

Gene Regulatory

Vertices and edges are made from a network, with the degree of a vertex referring to the number of connected edges. The chance of every vertex possessing a given degree is represented by a network’s degree appropriation, which reveals important global network characteristics. Many fields, including sociology, public health, business, medicine, engineering, computer science, and basic sciences, use network theory. Logistical networks, gene regulatory networks, metabolic networks, social networks, and driven networks are some of the most significant networks. In physical, theoretical, and environmental chemistry, a topological index is a numerical value assigned to a molecular structure/network that is used for correlation analysis. Hexagonal networks of dimension t are used to build hex-derived networks, which have a wide range of applications in computer science, medicine, and engineering. For the third type of hex-derived networks, topological indices of reverse degree based are discussed in this study.

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ENDOGENOUS RETROVIRUSES AS GENETIC MODULES THAT SHAPE THE GENOME REGULATORY NETWORKS DURING EVOLUTION

The Journal of V. N. Karazin Kharkiv National University, Series "Medicine" ◽

10.26565/2313-6693-2018-36-12 ◽

2018 ◽

Keyword(s):

Regulatory Networks ◽

Gene Activation ◽

Cell Types ◽

Regulatory Elements ◽

Endogenous Retroviruses ◽

Protein Coding ◽

Transcriptional Enhancers ◽

Wide Range ◽

Gene Regulatory Elements ◽

Gene Regulatory

Endogenous retroviruses (ERV) are the descendants of exogenous retroviruses that integrated into the germ cells genome, fixed and became inheritable. ERVs have evolved transcriptional enhancers and promoters that allow their replication in a wide range of tissue. Because ERVs comprise the regulatory elements it could be assume that ERVs capable to shape and reshape genomic regulatory networks by inserting their promoters and enhancers in new genomic loci upon retrotransposition. Thus retroransposition events can build new regulatory regions and lead to a new pattern of gene activation in the cell. In this review we summarize evidence which revealed that ERVs provide a plethora of novel gene regulatory elements, including tissue specific promoters and enhancers for protein-coding genes or long noncoding RNAs in a wide range of cell types. The accumulated findings support the hypothesis that the ERVs have rewired the gene regulatory networks and act as a major source of genomic regulatory innovation during evolution.

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AGL16 regulates genome-wide gene expression and flowering time with partial dependency on SOC1 in Arabidopsis

10.1101/2021.05.10.443448 ◽

2021 ◽

Author(s):

Xue Dong ◽

Li-Ping Zhang ◽

Dongmei Yu ◽

Fang Cheng ◽

Yinxin Dong ◽

...

Keyword(s):

Gene Expression ◽

Flowering Time ◽

Regulatory Networks ◽

Binding Property ◽

Loss Of Function ◽

Genome Wide ◽

Carg Box ◽

Gene Regulatory ◽

Genome Wide Gene Expression

Flowering transition is pivotal and tightly regulated by complex gene-regulatory-networks, in which AGL16 plays important roles. But the molecular function and binding property of AGL16 is not fully explored in vivo. With ChIP-seq and comparative transcriptomics approaches, we characterized the AGL16 targets spectrum and tested its close molecular and genetic interactions with SOC1, the key flowering integrator. AGL16 bound to promoters of more than 2000 genes via CArG-box motifs that were highly similar to that of SOC1. Being consistent with this, AGL16 formed protein complex and shared a common set of targets with SOC1. However, only very few genes showed differential expression in the agl16-1 loss-of-function mutant, whereas in the soc1-2 knockout background, AGL16 repressed and activated the expression of 375 and 182 genes, respectively, with more than a quarter of the DEGs were also bound by AGL16. AGL16 targeted potentially to about seventy flowering time genes involved in multiple pathways. Corroborating with these, AGL16 repressed the flowering time stronger in soc1-2 than in Col-0 background. These data reveals that AGL16 regulates gene expression and flowering time with a partial dependency on SOC1 activity. Moreover, AGL16 participated in the regulation of water loss and seed dormancy. Our study thus defines the AGL16 molecular spectrum and provides insights underlining the molecular coordination of flowering and environmental adaptation.

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A robust mathematical model of adaxial-abaxial patterning

in silico Plants ◽

10.1093/insilicoplants/diaa015 ◽

2020 ◽

Author(s):

Luke Andrejek ◽

Ching-Shan Chou ◽

Aman Husbands

Keyword(s):

Small Rna ◽

Regulatory Networks ◽

Model Parameters ◽

Leaf Architecture ◽

Dynamic Interactions ◽

Leaf Production ◽

Wide Range ◽

Gene Regulatory ◽

Biological Development ◽

Robust To Noise

Abstract Biological development results from intricate and dynamic interactions between members of gene regulatory networks. This is exemplified by the production of flat leaf architecture. Leaves flatten by driving growth along the boundary between their adaxial (top) and abaxial (bottom) domains. These domains are generated by interactions between a complex network of transcription factors and small RNAs. Despite its complexity, flat leaf production is robust to genetic and environmental noise. To identify factors contributing to this robustness, we mathematically modeled the determinants and interactions that pattern the adaxial-abaxial axis in leaves of Arabidopsis thaliana. Model parameters were estimated almost exclusively using experimental data. Our model recapitulates observations of adaxial-abaxial patterning and small RNA-target interactions. Positioning of the adaxial-abaxial boundary is stable across a wide range of small RNA source values and is highly robust to noise in the model. The successful application of our one-dimensional spatial model will enable higher-dimension modeling of the complex and mechanistically challenging process of flat leaf production.

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Trophoblast development

Reproduction ◽

10.1530/rep-11-0374 ◽

2012 ◽

Vol 143 (3) ◽

pp. 231-246 ◽

Cited By ~ 45

Author(s):

Peter L Pfeffer ◽

David J Pearton

Keyword(s):

Regulatory Networks ◽

Current Knowledge ◽

Embryonic Stem ◽

Loss Of Function ◽

Expression Studies ◽

Gene Regulatory ◽

Gene Expression Studies ◽

Function Models

This review summarises current knowledge about the specification, commitment and maintenance of the trophoblast lineage in mice and cattle. Results from gene expression studies, in vivo loss-of-function models and in vitro systems using trophoblast and embryonic stem cells have been assimilated into a model seeking to explain trophoblast ontogeny via gene regulatory networks. While trophoblast differentiation is quite distinct between cattle and mice, as would be expected from their different modes of implantation, recent studies have demonstrated that differences arise much earlier during trophoblast development.

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