Modeling transcriptional networks in Drosophila development at multiple scales

Wunderlich, Zeba; DePace, Angela H.

doi:10.1016/j.gde.2011.07.005

Cited by 29 publications

(23 citation statements)

References 50 publications

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“…Programs of differential gene expression can be viewed as dynamic networks of regulatory genes (genes that encode transcription factors, or TFs), and the cisregulatory DNA elements to which TFs bind. Such gene regulatory networks (GRNs) are proving to be powerful tools for analyzing cell specification and the evolution of development (Stathopoulos and Levine, 2005;Davidson, 2010;Peter and Davidson, 2011;Van Nostrand and Kim, 2011;Wunderlich and DePace, 2011). A current limitation of this conceptual approach to development, however, is that we have a poor understanding of the connections between transcriptional networks and the morphogenetic processes that build tissues and organs.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins

Azhari¹,

Shashikant²,

McManus³

et al. 2014

Development

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There was an error published in Development 141, 950-961.Column M of supplementary Table S1 contained an error and has been replaced. The authors apologise to readers for this mistake. ABSTRACT A central challenge of developmental and evolutionary biology is to understand the transformation of genetic information into morphology. Elucidating the connections between genes and anatomy will require model morphogenetic processes that are amenable to detailed analysis of cell/tissue behaviors and to systems-level approaches to gene regulation. The formation of the calcified endoskeleton of the sea urchin embryo is a valuable experimental system for developing such an integrated view of the genomic regulatory control of morphogenesis. A transcriptional gene regulatory network (GRN) that underlies the specification of skeletogenic cells (primary mesenchyme cells, or PMCs) has recently been elucidated. In this study, we carried out a genome-wide analysis of mRNAs encoded by effector genes in the network and uncovered transcriptional inputs into many of these genes. We used RNA-seq to identify >400 transcripts differentially expressed by PMCs during gastrulation, when these cells undergo a striking sequence of behaviors that drives skeletal morphogenesis. Our analysis expanded by almost an order of magnitude the number of known (and candidate) downstream effectors that directly mediate skeletal morphogenesis. We carried out genome-wide analysis of (1) functional targets of Ets1 and Alx1, two pivotal, early transcription factors in the PMC GRN, and (2) functional targets of MAPK signaling, a pathway that plays an essential role in PMC specification. These studies identified transcriptional inputs into >200 PMC effector genes. Our work establishes a framework for understanding the genomic regulatory control of a major morphogenetic process and has important implications for reconstructing the evolution of biomineralization in metazoans. 2542

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Section: Introductionmentioning

confidence: 99%

Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins

Azhari¹,

Shashikant²,

McManus³

et al. 2014

Development

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“…Analysis of transcriptional regulation in Drosophila has provided a mainstay for efforts to understand regulatory systems on an organismic level. Foundational studies focused on subsystems (both cis-regulatory elements and their collaborating trans-acting factors) controlling aspects of early developmental patterning (Hong et al 2008;Wunderlich and DePace 2011). More recently, the advent of system-wide methodologies coupled with high-throughput sequencing technology has fueled the genome-wide analysis of nucleosome occupancy, chromatin modification states, insulator elements, transcription factor (TF) and RNA polymerase II binding sites, and tissue and temporal gene expression patterns (MacArthur et al 2009;Schuettengruber et al 2009;Negre et al 2010Negre et al , 2011Roy et al 2010;Graveley et al 2011;Kaplan et al 2011;Kharchenko et al 2011;Li et al 2011;The ENCODE Project Consortium 2012).…”

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confidence: 99%

Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

et al. 2013

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Cys 2 -His 2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have characterized the DNA-binding specificities of 129 zinc finger sets from Drosophila using a bacterial one-hybrid system. This data set contains the DNA-binding specificities for at least one encoded ZFP from 70 unique genes and 23 alternate splice isoforms representing the largest set of characterized ZFPs from any organism described to date. These recognition motifs can be used to predict genomic binding sites for these factors within the fruit fly genome. Subsets of fingers from these ZFPs were characterized to define their orientation and register on their recognition sequences, thereby allowing us to define the recognition diversity within this finger set. We find that the characterized fingers can specify 47 of the 64 possible DNA triplets. To confirm the utility of our finger recognition models, we employed subsets of Drosophila fingers in combination with an existing archive of artificial zinc finger modules to create ZFPs with novel DNA-binding specificity. These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes.

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“…Second, following the step of data fusion, one can attempt to model the observed multivariable dynamics. Here one can employ several modeling methodologies, from mechanistic modeling of specific molecular and tissue-level processes [31][32][33][34][35], to equationfree approaches, which aim to deduce the underlying mechanisms directly from data [36,37].…”

Section: Discussionmentioning

confidence: 99%

Synthesizing developmental trajectories

Villoutreix

Andén

Lim

et al. 2017

Preprint

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Dynamical processes in biology are studied using an ever-increasing number of techniques, each of which brings out unique features of the system. One of the current challenges is to develop systematic approaches for fusing heterogeneous datasets into an integrated view of multivariable dynamics. We demonstrate that heterogeneous data fusion can be successfully implemented within a semi-supervised learning framework that exploits the intrinsic geometry of high-dimensional datasets. We illustrate our approach using a dataset from studies of pattern formation in Drosophila. The result is a continuous trajectory that reveals the joint dynamics of gene expression, subcellular protein localization, protein phosphorylation, and tissue morphogenesis. Our approach can be readily adapted to other imaging modalities and forms a starting point for further steps of data analytics and modeling of biological dynamics. Author summaryA wide range of problems in biology require analysis of multivariable dynamics in space and time. As a rule, the multiscale nature and complexity of real systems precludes simultaneous monitoring of all the relevant variables, and multivariable dynamics must be synthesized from partial views provided by different experimental techniques. We present a formal framework for accomplishing this task in the context of imaging studies of pattern formation in developing tissues.

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Modeling transcriptional networks in Drosophila development at multiple scales

Cited by 29 publications

References 50 publications

Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins

Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins

Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

Synthesizing developmental trajectories

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Modeling transcriptional networks in Drosophila development at multiple scales

Cited by 29 publications

References 50 publications

Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins

Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins

Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

Synthesizing developmental trajectories

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Product

Resources

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Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants