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The synthesis of gene expression data and cis-regulatory analysis permits the elucidation of genomic regulatory networks. These networks provide a direct visualization of the functional interconnections among the regulatory genes and signaling components leading to cell-specific patterns of gene activity. Complex developmental processes are thereby illuminated in ways not revealed by the conventional analysis of individual genes. In this review, we describe emerging networks in several different model systems, and compare them with the gene regulatory network that controls dorsoventral patterning of the Drosophila embryo. 相似文献
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Rubel Oliver Weber Gunther H. Huang Min-Yu Bethel E. Wes Biggin Mark D. Fowlkes Charless C. Luengo Hendriks Cris L. Keranen Soile V. E. Eisen Michael B. Knowles David W. Malik Jitendra Hagen Hans Hamann Bernd 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2010,7(1):64-79
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Three-dimensional digital mouse atlas using high-resolution MRI 总被引:9,自引:0,他引:9
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Tissue-Specific Expression Phenotypes of Hawaiian Drosophila Adh Genes in Drosophila Melanogaster Transformants 总被引:4,自引:2,他引:2
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Interspecific differences in the tissue-specific patterns of expression displayed by the alcohol dehydrogenase (Adh) genes within the Hawaiian picture-winged Drosophila represent a rich source of evolutionary variation in gene regulation. Study of the cis-acting elements responsible for regulatory differences between Adh genes from various species is greatly facilitated by analyzing the behavior of the different Adh genes in a homogeneous background. Accordingly, the Adh gene from Drosophila grimshawi was introduced into the germ line of Drosophila melanogaster by means of P element-mediated transformation, and transformants carrying this gene were compared to transformants carrying the Adh genes from Drosophila affinidisjuncta and Drosophila hawaiiensis. The results indicate that the D. affinidisjuncta and D. grimshawi genes have relatively higher levels of expression and broader tissue distribution of expression than the D. hawaiiensis gene in larvae. All three genes are expressed at similar overall levels in adults, with differences in tissue distribution of enzyme activity corresponding to the pattern in the donor species. However, certain systematic differences between Adh gene expression in transformants and in the Hawaiian Drosophila are noted along with tissue-specific position effects in some cases. The implications of these findings for the understanding of evolved regulatory variation are discussed. 相似文献
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Lott SE Ludwig MZ Kreitman M 《Evolution; international journal of organic evolution》2011,65(5):1388-1399
Pattern formation in Drosophila is a widely studied example of a robust developmental system. Such robust systems pose a challenge to adaptive evolution, as they mask variation that selection may otherwise act upon. Yet we find variation in the localization of expression domains (henceforth "stripe allometry") in the pattern formation pathway. Specifically, we characterize differences in the gap genes giant and Kruppel, and the pair-rule gene even-skipped, which differ between the sibling species Drosophila simulans and D. sechellia. In a double-backcross experiment, stripe allometry is consistent with maternal inheritance of stripe positioning and multiple genetic factors, with a distinct genetic basis from embryo length. Embryos produced by F1 and F2 backcross mothers exhibit novel spatial patterns of gene expression relative to the parental species, with no measurable increase in positional variance among individuals. Buffering of novel spatial patterns in the backcross genotypes suggests that robustness need not be disrupted in order for the trait to evolve, and perhaps the system is incapable of evolving to prevent the expression of all genetic variation. This limitation, and the ability of natural selection to act on minute genetic differences that are within the "margin of error" for the buffering mechanism, indicates that developmentally buffered traits can evolve without disruption of robustness. 相似文献
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Drosophila "gap" genes provide the first response to maternal gradients in the early fly embryo. Gap genes are expressed in a series of broad bands across the embryo during first hours of development. The gene network controlling the gap gene expression patterns includes inputs from maternal gradients and mutual repression between the gap genes themselves. In this study we propose a modular design for the gap gene network, involving two relatively independent network domains. The core of each network domain includes a toggle switch corresponding to a pair of mutually repressive gap genes, operated in space by maternal inputs. The toggle switches present in the gap network are evocative of the phage lambda switch, but they are operated positionally (in space) by the maternal gradients, so the synthesis rates for the competing components change along the embryo anterior-posterior axis. Dynamic model, constructed based on the proposed principle, with elements of fractional site occupancy, required 5-7 parameters to fit quantitative spatial expression data for gap gradients. The identified model solutions (parameter combinations) reproduced major dynamic features of the gap gradient system and explained gap expression in a variety of segmentation mutants. 相似文献
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Krüppel (Kr), a gap gene of Drosophila, shows complex spatial patterns of expression during the different stages of embryogenesis. In order to identify cis-acting sequences required for normal Kr gene expression, we analysed the expression patterns of fusion gene constructs in transgenic embryos. In these constructs, bacterial lacZ expression was placed under the control of Kr sequences in front of a basal promoter. We identified cis-acting Kr control units which drive beta-galactosidase expression in 10 known locations of Kr expression in early and late embryos. More than one cis-regulatory element drives the expression in the anterior domain at the blastoderm stage, in the nervous system, the midline precursor cells and in the amino-serosa. In addition, two cis-acting elements direct the first zygotic expression of Kr in a striped subpattern within the central region of the blastoderm embryo. Both elements respond to alterations in the activities of maternal organizer genes known to be required for Kr expression in establishing the thoracic and anterior abdominal segments in the wild-type embryo. 相似文献
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The interactions between the products of gap genes and pair-rule promoters results in the single most dramatic increase in the spatial complexity of gene expression during the segmentation process. We attempt to relate recent findings on the regulation of striped patterns of gene expression in the early Drosophila embryo to general strategies of gene expression and development employed by higher organisms. 相似文献
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David L. Stern Nicolás Frankel 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2013,368(1632)
In this paper, we provide a historical account of the contribution of a single line of research to our current understanding of the structure of cis-regulatory regions and the genetic basis for morphological evolution. We revisit the experiments that shed light on the evolution of larval cuticular patterns within the genus Drosophila and the evolution and structure of the shavenbaby gene. We describe the experiments that led to the discovery that multiple genetic changes in the cis-regulatory region of shavenbaby caused the loss of dorsal cuticular hairs (quaternary trichomes) in first instar larvae of Drosophila sechellia. We also discuss the experiments that showed that the convergent loss of quaternary trichomes in D. sechellia and Drosophila ezoana was generated by parallel genetic changes in orthologous enhancers of shavenbaby. We discuss the observation that multiple shavenbaby enhancers drive overlapping patterns of expression in the embryo and that these apparently redundant enhancers ensure robust shavenbaby expression and trichome morphogenesis under stressful conditions. All together, these data, collected over 13 years, provide a fundamental case study in the fields of gene regulation and morphological evolution, and highlight the importance of prolonged, detailed studies of single genes. 相似文献
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Flynn CJ Sharma T Ruffins SW Guerra SL Crowley JC Ettensohn CA 《Developmental biology》2011,(2):532-540
The analysis of temporal and spatial patterns of gene expression is critically important for many kinds of developmental studies, including the construction of gene regulatory networks. Recently, multiplex, fluorescent, whole mount in situ hybridization (multiplex F-WMISH), applied in combination with confocal microscopy, has emerged as the method of choice for high-resolution, three-dimensional (3D) mapping of gene expression patterns in developing tissues. We have developed an image analysis tool, GeneExpressMap (GEM), that facilitates the rapid, 3D analysis of multiplex F-WMISH data at single-cell resolution. GEM assigns F-WMISH signal to individual cells based upon the proximity of cytoplasmic hybridization signal to cell nuclei. Here, we describe the features of GEM and, as a test of its utility, we use GEM to analyze patterns of regulatory gene expression in the non-skeletogenic mesoderm of the early sea urchin embryo. GEM greatly extends the power of multiplex F-WMISH for analyzing patterns of gene expression and is a valuable tool for gene network analysis and many other kinds of developmental studies. 相似文献
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Comparison of the gap segmentation gene hunchback between Drosophila melanogaster and Drosophila virilis reveals novel modes of evolutionary change. 总被引:20,自引:4,他引:16
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We have cloned and sequenced a large portion of the hunchback (hb) locus from Drosophila virilis. Comparison with the Drosophila melanogaster hb sequence shows multiple strong homologies in the upstream and downstream regions of the gene, including most of the known functional parts. The coding sequence is highly conserved within the presumptive DNA-binding finger regions, but more diverged outside of them. The regions of high divergence are correlated with regions which are rich in short direct repeats (regions of high 'cryptic simplicity'), suggesting a significant influence of slippage-like mechanisms in the evolutionary divergence of the two genes. Staining of early D.virilis embryos with an hb antibody reveals conserved and divergent features of the spatial expression pattern at blastoderm stage. It appears that the basic expression pattern, which serves as the gap gene function of hb, is conserved, while certain secondary expression patterns, which have separate functions for the segmentation process, are partly diverged. Thus, both slippage driven mutations in the coding region, which are likely to occur at higher rates than point mutations and the evolutionary divergence of secondary expression patterns may contribute to the evolution of regulatory genes. 相似文献
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Embryonic development is driven by spatial patterns of gene expression that determine the fate of each cell in the embryo. While gene expression is often highly erratic, embryonic development is usually exceedingly precise. In particular, gene expression boundaries are robust not only against intra-embryonic fluctuations such as noise in gene expression and protein diffusion, but also against embryo-to-embryo variations in the morphogen gradients, which provide positional information to the differentiating cells. How development is robust against intra- and inter-embryonic variations is not understood. A common motif in the gene regulation networks that control embryonic development is mutual repression between pairs of genes. To assess the role of mutual repression in the robust formation of gene expression patterns, we have performed large-scale stochastic simulations of a minimal model of two mutually repressing gap genes in Drosophila, hunchback (hb) and knirps (kni). Our model includes not only mutual repression between hb and kni, but also the stochastic and cooperative activation of hb by the anterior morphogen Bicoid (Bcd) and of kni by the posterior morphogen Caudal (Cad), as well as the diffusion of Hb and Kni between neighboring nuclei. Our analysis reveals that mutual repression can markedly increase the steepness and precision of the gap gene expression boundaries. In contrast to other mechanisms such as spatial averaging and cooperative gene activation, mutual repression thus allows for gene-expression boundaries that are both steep and precise. Moreover, mutual repression dramatically enhances their robustness against embryo-to-embryo variations in the morphogen levels. Finally, our simulations reveal that diffusion of the gap proteins plays a critical role not only in reducing the width of the gap gene expression boundaries via the mechanism of spatial averaging, but also in repairing patterning errors that could arise because of the bistability induced by mutual repression. 相似文献
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cis-regulatory DNA sequences known as enhancers control gene expression in space and time. They are central to metazoan development and are often responsible for changes in gene regulation that contribute to phenotypic evolution. Here, we examine the sequence, function, and genomic location of enhancers controlling tissue- and cell-type specific expression of the yellow gene in six Drosophila species. yellow is required for the production of dark pigment, and its expression has evolved largely in concert with divergent pigment patterns. Using Drosophila melanogaster as a transgenic host, we examined the expression of reporter genes in which either 5' intergenic or intronic sequences of yellow from each species controlled the expression of Green Fluorescent Protein. Surprisingly, we found that sequences controlling expression in the wing veins, as well as sequences controlling expression in epidermal cells of the abdomen, thorax, and wing, were located in different genomic regions in different species. By contrast, sequences controlling expression in bristle-associated cells were located in the intron of all species. Differences in the precise pattern of spatial expression within the developing epidermis of D. melanogaster transformants usually correlated with adult pigmentation in the species from which the cis-regulatory sequences were derived, which is consistent with cis-regulatory evolution affecting yellow expression playing a central role in Drosophila pigmentation divergence. Sequence comparisons among species favored a model in which sequential nucleotide substitutions were responsible for the observed changes in cis-regulatory architecture. Taken together, these data demonstrate frequent changes in yellow cis-regulatory architecture among Drosophila species. Similar analyses of other genes, combining in vivo functional tests of enhancer activity with in silico comparative genomics, are needed to determine whether the pattern of regulatory evolution we observed for yellow is characteristic of genes with rapidly evolving expression patterns. 相似文献
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Vertebrate homeobox genes of the Hox family are, like Drosophila homeotic genes, organized in gene clusters and show a strict correspondence, or collinearity, between the order of the genes (3' to 5') within the chromosomal cluster and that of their expression domains (anterior to posterior) in the embryo. Recent data obtained from embryonal carcinoma cells induced to differentiate by retinoic acid cast some light on the molecular mechanisms underlying the collinear expression of the Hox genes. 相似文献