Global Gene Expression Analysis of Murine Limb Development
Publication Date
December 09, 2011
Journal
PLOS ONE
Authors
Leila Taher, Nicole M. Collette, Deepa Murugesh, Evan Maxwell, et al
Volume
6
Issue
12
Pages
e28358
DOI
https://dx.plos.org/10.1371/journal.pone.0028358
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0028358
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22174793
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235105
Europe PMC
http://europepmc.org/abstract/MED/22174793
Web of Science
000298365700028
Scopus
83055182201
Mendeley
http://www.mendeley.com/research/global-gene-expression-analysis-murine-limb-development-2
Events
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Mendeley | Further Information

{"title"=>"Global gene expression analysis of murine limb development", "type"=>"journal", "authors"=>[{"first_name"=>"Leila", "last_name"=>"Taher", "scopus_author_id"=>"6507061443"}, {"first_name"=>"Nicole M.", "last_name"=>"Collette", "scopus_author_id"=>"6602733125"}, {"first_name"=>"Deepa", "last_name"=>"Murugesh", "scopus_author_id"=>"6507236812"}, {"first_name"=>"Evan", "last_name"=>"Maxwell", "scopus_author_id"=>"54581320500"}, {"first_name"=>"Ivan", "last_name"=>"Ovcharenko", "scopus_author_id"=>"7004260592"}, {"first_name"=>"Gabriela G.", "last_name"=>"Loots", "scopus_author_id"=>"6604082598"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-83055182201", "sgr"=>"83055182201", "pui"=>"363060376", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "pmid"=>"22174793", "doi"=>"10.1371/journal.pone.0028358"}, "id"=>"76f16523-2b32-3862-bdc1-9afd19260ea6", "abstract"=>"Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature and nerves are specified and the musculoskeletal system of limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore- and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which levels off at later time points. Among the 3520 genes identified as significantly up-regulated in the limb, we find ~30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that are likely to correlate with functional programs during limb development and further characterization of these transcripts will provide new insights into specific tissue patterning processes. Here, we provide for the first time a comprehensive analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis.", "link"=>"http://www.mendeley.com/research/global-gene-expression-analysis-murine-limb-development-2", "reader_count"=>92, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Librarian"=>1, "Researcher"=>28, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>32, "Student > Master"=>12, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Librarian"=>1, "Researcher"=>28, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>32, "Student > Master"=>12, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>4, "Biochemistry, Genetics and Molecular Biology"=>22, "Agricultural and Biological Sciences"=>51, "Medicine and Dentistry"=>8, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Sports and Recreations"=>1, "Physics and Astronomy"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>4}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>51}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>22}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>1, "Australia"=>1, "Portugal"=>1, "Germany"=>1, "India"=>1}, "group_count"=>4}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/703878"], "description"=>"<p>Fore- and hind-limb buds were cut away from the embryo body as indicated by the red dash and RNA was processed from the full appendages outlined for stages E9.5 to E13.5. Light blue indicate mesenchymal condensations, and cartilage as determined by alcian blue staining is marked by thick black lines. Hindlimbs are morphologically delayed by ∼half a day.</p>", "links"=>[], "tags"=>["bud"], "article_id"=>374240, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Limb_Bud_Morphology_/374240", "title"=>"Limb Bud Morphology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-09 01:10:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/704430"], "description"=>"<p>Here we graphically depict the change in cell types and tissue formation as a function of developmental stage, highlighting key events during bone, muscle, nerve and skin formation (A). Some key molecules known to participate in these processes are also included along with the cell type morphologies for different stages of skeletal development. GO analysis identified several enrichment categories including osteoblast differentiation (B), epithelial differentiation (C), anterior-posterior patterning (D), neuronal differentiation (E), digit morphogenesis (F), epithelial to mesenchymal transition (G), cartilage development (H), embryonic skeletal system morphogenesis (I) and limb morphogenesis (J). For each plot log2 intensity is on the y axis, and developmental stages are on the x-axis. For each gene the solid trace depicts limb expression and the dashed trace depicts expression found in the whole embryo. Each gene corresponds to a different symbol along the traces.</p>", "links"=>[], "tags"=>["events", "corresponding", "stages", "enrichments"], "article_id"=>374786, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentiation_Events_Corresponding_to_Stages_of_Limb_Development_and_Functional_Category_Enrichments_that_Describe_some_of_these_Events_/374786", "title"=>"Differentiation Events Corresponding to Stages of Limb Development and Functional Category Enrichments that Describe some of these Events.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-09 01:19:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/703982"], "description"=>"<p>279 genes were examined for their putative protein function, available <i>in situ</i> expression in the limb, and description of null mouse phenotype (A). Most known genes previously uncharacterized in the limb with (B), or novel genes (C) showed unique and restrictive expression pattern in the limb. A survey of <i>in situs</i> of known genes with musculoskeletal defects in the knockout mouse are in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028358#pone.0028358.s001\" target=\"_blank\">Figure S1</a>.</p>", "links"=>[], "tags"=>["100", "up-regulated"], "article_id"=>374339, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_the_Top_100_Up_regulated_Genes_/374339", "title"=>"Analysis of the Top 100 Up-regulated Genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-09 01:12:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/704608"], "description"=>"<p>1140 transcripts were found to be significantly up-regulated exclusively at one developmental time point. A large fraction of these stage specific genes were found to be novel (A), in particular at E13.5 only 5% of the transcripts had confirmed musculoskeletal knockout phenotypes and 6% of the genes have been validated by <i>in situ</i> hybridization. A survey of available <i>in situ</i> expression profiles for genes with peak expression levels at E9.5 (B), E10.5 (C), E11.5 (D), E12.5 (E) and E13.5 (F) revealed that they display a wide range of patterns, and include closely related members of gene families such as Irx, Smarc and zinc finger transcription factors.</p>", "links"=>[], "tags"=>["genetics and genomics", "molecular biology", "Computational biology", "developmental biology"], "article_id"=>374959, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_Stage_Specific_Gene_Expression_/374959", "title"=>"Analysis of Stage Specific Gene Expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-09 01:22:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/704824"], "description"=>"<p>To identify genes specifically enriched in the forelimb or hindlimb, we adjusted for the developmental delay of hindlimbs by comparing forelimbs to same stage hindlimbs as well as to hindlimbs from a subsequent time point (A). More forelimb enriched genes were identified (B), and the genes with >2 fold up-regulation in the forelimb (C) or hindlimb (D) are displayed. Genes previously known to function as a limb-identity determinant are marked by red arrows (<i>Tbx5</i>; <i>Hoxc10</i>, <i>Tbx4</i>, <i>Pitx1</i>).</p>", "links"=>[], "tags"=>["genes"], "article_id"=>375184, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identifying_Genes_that_Contribute_to_Limb_Identity_/375184", "title"=>"Identifying Genes that Contribute to Limb Identity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-09 01:26:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/704291"], "description"=>"<p>Clusters of co-transcribed genes were grouped into early genes (A), peak genes (B), late genes (C) and oscillating genes (D) based on their profiles. The number of genes corresponding to each curve are indicated below the trace.</p>", "links"=>[], "tags"=>["genetics and genomics", "molecular biology", "Computational biology", "developmental biology"], "article_id"=>374644, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.g004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Temporal_Expression_Pattern_Analysis_in_the_Developing_Forelimb_/374644", "title"=>"Temporal Expression Pattern Analysis in the Developing Forelimb.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-09 01:17:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/704192"], "description"=>"<p><i>C130021I20Rik</i> was mapped to the <i>Lmx1b</i> gene locus (A) and found to be transcribed on the opposite strand. Time course <i>in situ</i> analysis revealed that <i>C130021I20Rik</i> (C) expression pattern is indistinguishable from its neighbor, <i>Lmx1b</i> (B), in the dorsal mesenchyme (b–c) suggesting that they are transcribed from the same divergent promoter and share limb-specific regulatory elements.</p>", "links"=>[], "tags"=>["co-transcribed", "lmx1b"], "article_id"=>374549, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_C130021I20Rik_is_a_Novel_Gene_Co_transcribed_from_the_Lmx1b_Promoter_a_well_Known_Limb_Gene_/374549", "title"=>"C130021I20Rik is a Novel Gene Co-transcribed from the Lmx1b Promoter, a well Known Limb Gene.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-09 01:15:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/705155"], "description"=>"<p>8/15 clusters were identified to contain cohorts of functional related genes (p<0.05; >2-fold enrichment) primarily represented by transcription factors (clustes 1/2/5/12) and genes associated with limb/skeletal morphogenesis (clusters 1/2/5/6). ‘Gene count’ represents the number of genes in the cluster with the specified biological process or molecular function, while ‘total # genes’ represents the total number of genes present on the microarray within the same category. Enrichment is fold over background. Genes corresponding to GO enriched categories highlighted in brown are plotted in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028358#pone-0028358-g005\" target=\"_blank\">Figure 5</a>. BP biological process; MF molecular function.</p>", "links"=>[], "tags"=>["functionally", "genes", "groups", "co-expressed"], "article_id"=>375514, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.t002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Enrichment_of_functionally_related_genes_in_groups_of_co_expressed_genes_/375514", "title"=>"Enrichment of functionally related genes in groups of co-expressed genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-12-09 01:31:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/705195"], "description"=>"<p>A total of 6216 or 31.4% of gene symbols represented on the Affymetrix mouse array displayed expression changes in at least one pairwise comparison. All percentages displayed here are based on this total 6216 gene count. For both forelimbs (FL) and hindlimbs (HL) at each time point the number of up-regulated (>2X) and down-regulated (<2X) genes in relationship to whole embryo total RNA levels are indicated. Gene cohorts relevant to particular developmental stages were determined by comparing up-regulated genes between pairs of successive time points; genes exclusively up-regulated at each of the two time points considered (i.e., down-regulated or unchanged at the other) are indicated for each comparison (E9.5 vs E10.5; E10.5 vs E11.5; E11.5 vs E12.5 and E12.5 vs E13.5). Genes up-regulated only at one particular time point were identified by comparing the genes up-regulated at a given limb stage with those up-regulated at any other stage.</p>", "links"=>[], "tags"=>["genetics and genomics", "molecular biology", "Computational biology", "developmental biology"], "article_id"=>375551, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentially_Expressed_Genes_/375551", "title"=>"Differentially Expressed Genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-12-09 01:32:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/705000"], "description"=>"<p>Qualitatively some genes identified as forelimb or hindlimb specific do not appear to be restricted to one limb such as <i>Sp6</i>, <i>SmarcD2</i> and <i>Hoxc10</i>, yet quantitatively these transcripts are >2 fold up-regulated in one limb in relationship to the other.</p>", "links"=>[], "tags"=>["patterns", "fore-", "hind-limb"], "article_id"=>375356, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028358.g008", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_Patterns_of_Fore_and_Hind_limb_Specific_Genes_/375356", "title"=>"Expression Patterns of Fore- and Hind-limb Specific Genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-09 01:29:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/357526", "https://ndownloader.figshare.com/files/357571", "https://ndownloader.figshare.com/files/357597", "https://ndownloader.figshare.com/files/357635", "https://ndownloader.figshare.com/files/357807", "https://ndownloader.figshare.com/files/357984", "https://ndownloader.figshare.com/files/358236", "https://ndownloader.figshare.com/files/358422", "https://ndownloader.figshare.com/files/358434", "https://ndownloader.figshare.com/files/358464"], "description"=>"<div><p>Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature and nerves are specified and the musculoskeletal system of limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore- and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which levels off at later time points. Among the 3520 genes identified as significantly up-regulated in the limb, we find ∼30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that are likely to correlate with functional programs during limb development and further characterization of these transcripts will provide new insights into specific tissue patterning processes. Here, we provide for the first time a comprehensive analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis.</p> </div>", "links"=>[], "tags"=>["murine"], "article_id"=>130655, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Leila Taher", "Nicole M. Collette", "Deepa Murugesh", "Evan Maxwell", "Ivan Ovcharenko", "Gabriela G. Loots"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028358.s001", "https://dx.doi.org/10.1371/journal.pone.0028358.s002", "https://dx.doi.org/10.1371/journal.pone.0028358.s003", "https://dx.doi.org/10.1371/journal.pone.0028358.s004", "https://dx.doi.org/10.1371/journal.pone.0028358.s005", "https://dx.doi.org/10.1371/journal.pone.0028358.s006", "https://dx.doi.org/10.1371/journal.pone.0028358.s007", "https://dx.doi.org/10.1371/journal.pone.0028358.s008", "https://dx.doi.org/10.1371/journal.pone.0028358.s009", "https://dx.doi.org/10.1371/journal.pone.0028358.s010"], "stats"=>{"downloads"=>13, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Global_Gene_Expression_Analysis_of_Murine_Limb_Development/130655", "title"=>"Global Gene Expression Analysis of Murine Limb Development", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-12-09 00:10:55"}

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Relative Metric

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