Jamb and Jamc Are Essential for Vertebrate Myocyte Fusion
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{"title"=>"Jamb and jamc are essential for vertebrate myocyte fusion", "type"=>"journal", "authors"=>[{"first_name"=>"Gareth T.", "last_name"=>"Powell", "scopus_author_id"=>"19337605600"}, {"first_name"=>"Gavin J.", "last_name"=>"Wright", "scopus_author_id"=>"7402848863"}], "year"=>2011, "source"=>"PLoS Biology", "identifiers"=>{"pui"=>"364014876", "sgr"=>"84855161834", "issn"=>"15449173", "pmid"=>"22180726", "scopus"=>"2-s2.0-84855161834", "doi"=>"10.1371/journal.pbio.1001216", "isbn"=>"1545-7885 (Electronic)\\r1544-9173 (Linking)"}, "id"=>"beef83a3-7edf-3d0e-894e-f4a663a31701", "abstract"=>"Cellular fusion is required in the development of several tissues, including skeletal muscle. In vertebrates, this process is poorly understood and lacks an in vivo-validated cell surface heterophilic receptor pair that is necessary for fusion. Identification of essential cell surface interactions between fusing cells is an important step in elucidating the molecular mechanism of cellular fusion. We show here that the zebrafish orthologues of JAM-B and JAM-C receptors are essential for fusion of myocyte precursors to form syncytial muscle fibres. Both jamb and jamc are dynamically co-expressed in developing muscles and encode receptors that physically interact. Heritable mutations in either gene prevent myocyte fusion in vivo, resulting in an overabundance of mononuclear, but otherwise overtly normal, functional fast-twitch muscle fibres. Transplantation experiments show that the Jamb and Jamc receptors must interact between neighbouring cells (in trans) for fusion to occur. We also show that jamc is ectopically expressed in prdm1a mutant slow muscle precursors, which inappropriately fuse with other myocytes, suggesting that control of myocyte fusion through regulation of jamc expression has important implications for the growth and patterning of muscles. Our discovery of a receptor-ligand pair critical for fusion in vivo has important implications for understanding the molecular mechanisms responsible for myocyte fusion and its regulation in vertebrate myogenesis.", "link"=>"http://www.mendeley.com/research/jamb-jamc-essential-vertebrate-myocyte-fusion", "reader_count"=>41, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>6, "Librarian"=>1, "Researcher"=>13, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>10, "Student > Master"=>2, "Student > Bachelor"=>4, "Lecturer"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>6, "Librarian"=>1, "Researcher"=>13, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>10, "Student > Master"=>2, "Student > Bachelor"=>4, "Lecturer"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>30, "Medicine and Dentistry"=>2, "Business, Management and Accounting"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}}, "reader_count_by_country"=>{"Japan"=>1, "France"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/703904"], "description"=>"a<p>“n” denotes number of fibres, number of embryos analysed at 48 h. p. f. for each transplant experiment.</p>b<p>Translation blocking morpholino injected into donor before transplantation. n. d., not determined.</p>c<p>Minority fusion events are likely a result of incomplete morpholino knockdown, as seen in control transplants using <i>jamb<sup>HU3319</sup></i> or <i>jamc<sup>sa0037</sup></i> mutant hosts.</p>", "links"=>[], "tags"=>["fused", "unfused", "fluorescently", "labelled", "fibres", "transplanted"], "article_id"=>374261, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001216.t001", "stats"=>{"downloads"=>2, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantification_of_fused_multinucleated_and_unfused_mononucleated_fluorescently_labelled_fast_muscle_fibres_in_transplanted_hosts_/374261", "title"=>"Quantification of fused (multinucleated) and unfused (mononucleated) fluorescently labelled fast muscle fibres in transplanted hosts.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-12-13 01:11:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/703332"], "description"=>"<p>(A) Schematics of Jamb and Jamc extracellular proteins. Red stars denote sites of mutation in <i>HU3319</i> and <i>sa0037</i> alleles. (B–C) Confocal microscopy images of fast-twitch muscle in wild-type, <i>jamb<sup>HU3319</sup></i>, and <i>jamc<sup>sa0037</sup></i> 48 h. p. f. (B) and 120 h. p. f. (C) Embryos labelled with membrane targeted RFP (mRFP, cyan; B) or phalloidin-Alexa488 (cyan; C) and DAPI (red) show overabundant, mononuclear myofibres in both mutants. (D) Confocal microscopy images of uninjected, <i>jamb</i>, and <i>jamc</i> translation-blocking morpholino-injected wild-type embryos, stained with DAPI (red) and phalloidin-Alexa488 (cyan) to stain F-actin in fast muscle fibres. The morpholino-injected embryos replicate the <i>jam</i> mutants' phenotype. Myotomes 12–13 shown, anterior left. Scale bars represent 50 µm.</p>", "links"=>[], "tags"=>["myocyte", "fusion"], "article_id"=>373708, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001216.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_jamb_and_jamc_are_essential_for_myocyte_fusion_in_vivo_/373708", "title"=>"<i>jamb</i> and <i>jamc</i> are essential for myocyte fusion in vivo.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-13 01:01:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/703714"], "description"=>"<p>(A–D) Fluorescent dextran-labelled cells (magenta) from <i>jamb<sup>HU3319</sup></i> and <i>jamc<sup>sa0037</sup></i> donors can form multinucleate fibres with wild-type (A, B), <i>jamc<sup>sa0037</sup></i> (C), or <i>jamb<sup>HU3319</sup></i> (D) host cells, respectively. (E, F) Transplanted cells from doubly-deficient donors fail to fuse with wild-type host cells, suggesting both proteins are required and interact in trans. Confocal microscopy images from 48 h. p. f. embryos; anterior left. Schematics illustrate potential binding of Jamb and Jamc between donor (magenta) and host (green) cells in each experiment. bMO, cMO indicate <i>jamb</i> or <i>jamc</i> translation-blocking morpholino-injected donor embryos. Dotted lines indicate the position of myotome boundaries; arrowheads indicate nuclei within labelled fibres. Nuclei stained with DAPI (green). Scale bars represent 20 µm.</p>", "links"=>[], "tags"=>["trans", "myocyte"], "article_id"=>374084, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001216.g006", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Interaction_between_jamb_and_jamc_is_necessary_and_required_in_trans_for_myocyte_fusion_/374084", "title"=>"Interaction between <i>jamb</i> and <i>jamc</i> is necessary and required in trans for myocyte fusion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-13 01:08:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/703652"], "description"=>"<p>(A) Surface plasmon resonance experiments determine the equilibrium binding constant (<i>K</i><sub>D</sub>) for the heterophilic interaction between Jamb and Jamc (inset: sensorgrams showing equilibrium has been reached). (B) Dissociation rate constants and half-lives of homophilic and heterophilic interactions between recombinant extracellular domains of Jamb and Jamc. Curves represent a fit to a first-order decay, indicating a 1∶1 stoichiometry of binding. Dissociation data are the mean of three analyte concentrations for each interaction tested; error bars represent standard deviation.</p>", "links"=>[], "tags"=>["jamc"], "article_id"=>374022, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001216.g005", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Jamb_and_Jamc_physically_interact_/374022", "title"=>"Jamb and Jamc physically interact.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-13 01:07:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/703206"], "description"=>"<p>(A–B) Wholemount in situ hybridisation of <i>jamb</i> (A) and <i>jamc</i> (B) show expression in myoblasts during somitogenesis (10–13 somites, 17–18 somites, and 21 somites). Expression is attenuated in the myotome after the completion of primary myogenesis (24 h. p. f.) and then later upregulated in craniofacial (cf), pectoral fin (arrows), and hypaxial (open arrowheads) muscle mesoderm (48 h. p. f.). Scale bars represent 50 µm.</p>", "links"=>[], "tags"=>["co-expressed"], "article_id"=>373584, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001216.g001", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_jamb_and_jamc_are_co_expressed_in_myoblasts_/373584", "title"=>"<i>jamb</i> and <i>jamc</i> are co-expressed in myoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-13 00:59:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/703818"], "description"=>"<p>Wholemount in situ hybridisation against <i>jamc</i> (left panels), <i>jamb</i> (middle panels), and <i>kirrel3l</i> (right panels) shows that <i>jamc</i> is ectopically expressed in premigratory slow muscle precursors (adaxial cells) of <i>prdm1a<sup>tp39</sup></i> mutants that later inappropriately fuse to fast muscle myocytes. In contrast, <i>jamb</i> and <i>kirrel3l</i> are expressed in fast muscle myoblasts in both wild-type and <i>prdm1a<sup>tp39</sup></i> mutant embryos. Flatmounted embryos at 10–13 somite stage; anterior top.</p>", "links"=>[], "tags"=>["regulated"], "article_id"=>374186, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001216.g007", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_jamc_expression_is_regulated_by_prdm1a_/374186", "title"=>"<i>jamc</i> expression is regulated by <i>prdm1a</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-13 01:09:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/703508"], "description"=>"<p>(A) Superimposed confocal microscopy images of 24 h. p. f. wild-type, <i>jamb<sup>HU3319</sup></i>, and <i>jamc<sup>sa0037</sup></i> embryos stained with monoclonal antibody F59, which detects slow-muscle-specific myosin heavy chain (sMyHC), show normal slow muscle development in both mutants. (B) Single optical sections of 48 h. p. f. wild-type, <i>jamb<sup>HU3319</sup></i>, and <i>jamc<sup>sa0037</sup></i> embryos stained with monoclonal antibody EB165, which detects fast-muscle-specific myosin heavy chain (fMyHC), show that the medial mononuclear fibres in both mutants have differentiated as fast-twitch muscle. Myotomes 12–13 shown, anterior left. Scale bars represent 50 µm.</p>", "links"=>[], "tags"=>["slow-twitch", "fibres", "specified"], "article_id"=>373879, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001216.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fast_and_slow_twitch_muscle_fibres_are_correctly_specified_in_jamb_HU3319_and_jamc_sa0037_embryos_/373879", "title"=>"Fast and slow-twitch muscle fibres are correctly specified in <i>jamb<sup>HU3319</sup></i> and <i>jamc<sup>sa0037</sup></i> embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-13 01:04:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/357065", "https://ndownloader.figshare.com/files/357190", "https://ndownloader.figshare.com/files/357233", "https://ndownloader.figshare.com/files/357266", "https://ndownloader.figshare.com/files/357302", "https://ndownloader.figshare.com/files/357349"], "description"=>"<div><p>Cellular fusion is required in the development of several tissues, including skeletal muscle. In vertebrates, this process is poorly understood and lacks an in vivo-validated cell surface heterophilic receptor pair that is necessary for fusion. Identification of essential cell surface interactions between fusing cells is an important step in elucidating the molecular mechanism of cellular fusion. We show here that the zebrafish orthologues of JAM-B and JAM-C receptors are essential for fusion of myocyte precursors to form syncytial muscle fibres. Both <em>jamb</em> and <em>jamc</em> are dynamically co-expressed in developing muscles and encode receptors that physically interact. Heritable mutations in either gene prevent myocyte fusion in vivo, resulting in an overabundance of mononuclear, but otherwise overtly normal, functional fast-twitch muscle fibres. Transplantation experiments show that the Jamb and Jamc receptors must interact between neighbouring cells (in trans) for fusion to occur. We also show that <em>jamc</em> is ectopically expressed in <em>prdm1a</em> mutant slow muscle precursors, which inappropriately fuse with other myocytes, suggesting that control of myocyte fusion through regulation of <em>jamc</em> expression has important implications for the growth and patterning of muscles. Our discovery of a receptor-ligand pair critical for fusion in vivo has important implications for understanding the molecular mechanisms responsible for myocyte fusion and its regulation in vertebrate myogenesis.</p> </div>", "links"=>[], "tags"=>["jamb", "jamc", "are", "vertebrate", "myocyte", "fusion"], "article_id"=>130564, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001216.s001", "https://dx.doi.org/10.1371/journal.pbio.1001216.s002", "https://dx.doi.org/10.1371/journal.pbio.1001216.s003", "https://dx.doi.org/10.1371/journal.pbio.1001216.s004", "https://dx.doi.org/10.1371/journal.pbio.1001216.s005", "https://dx.doi.org/10.1371/journal.pbio.1001216.s006"], "stats"=>{"downloads"=>13, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Jamb_and_Jamc_Are_Essential_for_Vertebrate_Myocyte_Fusion/130564", "title"=>"Jamb and Jamc Are Essential for Vertebrate Myocyte Fusion", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-12-13 00:09:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/703579"], "description"=>"<p>(A) Transverse sections projected from confocal microscopy images of 48 h. p. f. embryos labelled with mRFP. (B–C) Graphs showing a significant overabundance (1.6–1.8-fold) of muscle fibres in mutants compared to wild-type (B) and calculated muscle nuclei number in wild-type and mutant embryos between 24 and 48 h. p. f. (C). Asterisk denotes <i>p</i>≤0.001; one-tailed Student's <i>t</i> test; error bars represent standard deviation, see <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001216#pbio.1001216.s005\" target=\"_blank\">Tables S1</a> and <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001216#pbio.1001216.s006\" target=\"_blank\">S2</a> for number of embryos in each sample.</p>", "links"=>[], "tags"=>["fibres", "supernumary"], "article_id"=>373953, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Gareth T. Powell", "Gavin J. Wright"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001216.g004", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fast_muscle_fibres_are_supernumary_in_jamb_HU3319_and_jamc_sa0037_embryos_/373953", "title"=>"Fast muscle fibres are supernumary in <i>jamb<sup>HU3319</sup></i> and <i>jamc<sup>sa0037</sup></i> embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-13 01:05:53"}

PMC Usage Stats | Further Information

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Relative Metric

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