Transcriptional Response of Zebrafish Embryos Exposed to Neurotoxic Compounds Reveals a Muscle Activity Dependent hspb11 Expression
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{"title"=>"Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression", "type"=>"journal", "authors"=>[{"first_name"=>"Nils", "last_name"=>"Klüver", "scopus_author_id"=>"8615817400"}, {"first_name"=>"Lixin", "last_name"=>"Yang", "scopus_author_id"=>"55732936200"}, {"first_name"=>"Wibke", "last_name"=>"Busch", "scopus_author_id"=>"26430503500"}, {"first_name"=>"Katja", "last_name"=>"Scheffler", "scopus_author_id"=>"57197003259"}, {"first_name"=>"Patrick", "last_name"=>"Renner", "scopus_author_id"=>"54783329900"}, {"first_name"=>"Uwe", "last_name"=>"Strähle", "scopus_author_id"=>"7004805378"}, {"first_name"=>"Stefan", "last_name"=>"Scholz", "scopus_author_id"=>"23029105100"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-83655183768", "pmid"=>"22205996", "sgr"=>"83655183768", "doi"=>"10.1371/journal.pone.0029063", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"363105747"}, "id"=>"d5524e94-7da3-32c5-bdf4-00b9ba778460", "abstract"=>"Acetylcholinesterase (AChE) inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM), in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB) and 2,4-dinitrophenol (DNP). A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sop(fixe) mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR) activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds.", "link"=>"http://www.mendeley.com/research/transcriptional-response-zebrafish-embryos-exposed-neurotoxic-compounds-reveals-muscle-activity-depe", "reader_count"=>41, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>11, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>11, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Environmental Science"=>7, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>4, "Neuroscience"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>6}, "Environmental Science"=>{"Environmental Science"=>7}}, "reader_count_by_country"=>{"United States"=>1, "Poland"=>1, "South Africa"=>1, "Germany"=>1}, "group_count"=>7}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/701239"], "description"=>"<p>Expression pattern of <i>hspb11</i> at 18 hpf were detected in developing adaxial musculature (A–A″). During later developmental stages, at 24 hpf, <i>hspb11</i> mRNA transcripts were restricted to muscle pioneers (B and B′) and became only expressed in the notochord at 50 hpf (C). (A, B) lateral view, (A′) dorsal view and (A″ and B′) cross sections. Increased expression pattern in axial musculature was observed in APM exposed (D) and homozygous (−/−) <i>ache</i> mutant embryos (E). <i>Hspb11</i> expression in homozygous <i>sop<sup>fixe</sup>−/−</i> embryos (F and G) and heterozygous/wildtype (+/?) siblings (<i>H</i> and <i>I</i>).</p>", "links"=>[], "tags"=>["apm", "mutant"], "article_id"=>371616, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Nils Klüver", "Lixin Yang", "Wibke Busch", "Katja Scheffler", "Patrick Renner", "Uwe Strähle", "Stefan Scholz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029063.g004", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Developmental_hspb11_expression_pattern_in_wildtype_APM_exposed_ache_and_sop_fixe_mutant_embryos_/371616", "title"=>"Developmental <i>hspb11</i> expression pattern in wildtype, APM exposed, <i>ache</i> and <i>sop<sup>fixe</sup></i> mutant embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-19 00:26:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/701419"], "description"=>"<p>(A) qPCR <i>hspb11</i> expression analysis. (B) Wildtype <i>hspb11</i> expression pattern at 24 hpf. (C) MS222 treatment results in the loss of <i>hspb11</i> expression pattern at 24 hpf.</p>", "links"=>[], "tags"=>["skeletal", "contraction", "ms-222", "inhibits"], "article_id"=>371788, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Nils Klüver", "Lixin Yang", "Wibke Busch", "Katja Scheffler", "Patrick Renner", "Uwe Strähle", "Stefan Scholz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029063.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blocking_the_skeletal_muscle_contraction_with_MS_222_inhibits_developmental_hspb11_expression_/371788", "title"=>"Blocking the skeletal muscle contraction with MS-222 inhibits developmental <i>hspb11</i> expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-19 00:29:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/358950", "https://ndownloader.figshare.com/files/358995", "https://ndownloader.figshare.com/files/359068", "https://ndownloader.figshare.com/files/359112", "https://ndownloader.figshare.com/files/359176", "https://ndownloader.figshare.com/files/359244", "https://ndownloader.figshare.com/files/359306", "https://ndownloader.figshare.com/files/359327"], "description"=>"<div><p>Acetylcholinesterase (AChE) inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM), in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB) and 2,4-dinitrophenol (DNP). A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein <em>hspb11</em> was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, <em>ache</em> and <em>sop<sup>fixe</sup></em> mutant embryos revealed that <em>hspb11</em> expression was dependent on the nicotinic acetylcholine receptor (nAChR) activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of <em>hspb11</em> which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, <em>hspb11</em> was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds.</p> </div>", "links"=>[], "tags"=>["transcriptional", "zebrafish", "embryos", "exposed", "neurotoxic", "compounds", "reveals"], "article_id"=>130952, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Nils Klüver", "Lixin Yang", "Wibke Busch", "Katja Scheffler", "Patrick Renner", "Uwe Strähle", "Stefan Scholz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0029063.s001", "https://dx.doi.org/10.1371/journal.pone.0029063.s002", "https://dx.doi.org/10.1371/journal.pone.0029063.s003", "https://dx.doi.org/10.1371/journal.pone.0029063.s004", "https://dx.doi.org/10.1371/journal.pone.0029063.s005", "https://dx.doi.org/10.1371/journal.pone.0029063.s006", "https://dx.doi.org/10.1371/journal.pone.0029063.s007", "https://dx.doi.org/10.1371/journal.pone.0029063.s008"], "stats"=>{"downloads"=>7, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Transcriptional_Response_of_Zebrafish_Embryos_Exposed_to_Neurotoxic_Compounds_Reveals_a_Muscle_Activity_Dependent_hspb11_Expression/130952", "title"=>"Transcriptional Response of Zebrafish Embryos Exposed to Neurotoxic Compounds Reveals a Muscle Activity Dependent <em>hspb11</em> Expression", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-12-19 00:15:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/700954"], "description"=>"<p>APM exposures for (A) 24 h (26–50 hpf) and (B) 2 h (48–50 hpf). Concentrations are given in µM. Bars represent the relative gene expression as fold change of the respective untreated control as mean ± standard deviation of three independent replicate exposures. Control  =  ctrl. * P<0.05.</p>", "links"=>[], "tags"=>["induction", "zebrafish"], "article_id"=>371330, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Nils Klüver", "Lixin Yang", "Wibke Busch", "Katja Scheffler", "Patrick Renner", "Uwe Strähle", "Stefan Scholz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029063.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_APM_concentration_dependent_induction_of_hspb11_pdlim3b_and_socs3a_in_zebrafish_embryos_/371330", "title"=>"APM concentration dependent induction of <i>hspb11</i>, <i>pdlim3b</i> and <i>socs3a</i> in zebrafish embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-19 00:22:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/700847"], "description"=>"<p>(A) Wild-type zebrafish embryo axial musculature is highly birefringent at 72 hpf. (B) APM [6 µM] exposure from 12–72 hpf resulted in defects in the axial musculature, which are shown by a reduced birefringence at 72 hpf.</p>", "links"=>[], "tags"=>["ache", "apm", "resulted", "reduced"], "article_id"=>371215, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Nils Klüver", "Lixin Yang", "Wibke Busch", "Katja Scheffler", "Patrick Renner", "Uwe Strähle", "Stefan Scholz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029063.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Repression_of_AChE_activity_with_APM_resulted_in_a_reduced_birefringence_/371215", "title"=>"Repression of AChE activity with APM resulted in a reduced birefringence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-19 00:20:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/701689"], "description"=>"<p>(A, D and G) mmMO-<i>hspb11</i> injected embryos. (B, E and H) MO(ATG)-<i>hspb11</i> morphants. (C, F and I) MO(UTR)-<i>hspb11</i> morphants. (A–C) Phenotypic observations of morpholino injected embryos at 48 hpf. (D–E) Muscle organization determined with birefringence at 72 hpf. (G–I) Slow muscle myosin distribution at 72 hpf shown by immunofluorescence staining with antibody F59. Arrows indicate gaps in fiber distribution.</p>", "links"=>[], "tags"=>["hspb11", "myosin", "disorganization", "skeletal"], "article_id"=>372060, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Nils Klüver", "Lixin Yang", "Wibke Busch", "Katja Scheffler", "Patrick Renner", "Uwe Strähle", "Stefan Scholz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029063.g006", "stats"=>{"downloads"=>5, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Knockdown_of_Hspb11_results_in_slow_muscle_myosin_disorganization_in_skeletal_muscles_/372060", "title"=>"Knockdown of Hspb11 results in slow muscle myosin disorganization in skeletal muscles.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-19 00:34:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/701090"], "description"=>"<p>(A) <i>hspb11</i> expression analysis in <i>ache</i> and <i>sop<sup>fixe</sup>−/−</i> zebrafish mutant embryos at 48 hpf. (B) <i>hspb11</i> expression in <i>sop<sup>fixe</sup></i> null mutants and siblings (+/?  =  heterozygous and wildtype) after APM (6 µM) exposure (26–50 hpf). (C) 1 µM Thapsigargin (TG) and 2 mM caffeine (CAF) induce <i>hspb11</i> expression in zebrafish embryos (exposure period 48–50 hpf). Bars represent the relative gene expression as fold change of the respective untreated control as mean ± standard deviation of three independent replicate exposures Control  =  ctrl. * P<0.05.</p>", "links"=>[], "tags"=>["mediated", "induction", "depends", "nachr", "intracellular", "calcium"], "article_id"=>371460, "categories"=>["Neuroscience", "Genetics", "Developmental Biology"], "users"=>["Nils Klüver", "Lixin Yang", "Wibke Busch", "Katja Scheffler", "Patrick Renner", "Uwe Strähle", "Stefan Scholz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029063.g003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_APM_mediated_hspb11_induction_depends_on_nAChR_activity_and_increased_intracellular_calcium_levels_/371460", "title"=>"APM mediated <i>hspb11</i> induction depends on nAChR activity and increased intracellular calcium levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-19 00:24:20"}

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