Both the Caspase CSP-1 and a Caspase-Independent Pathway Promote Programmed Cell Death in Parallel to the Canonical Pathway for Apoptosis in Caenorhabditis elegans
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{"title"=>"Both the Caspase CSP-1 and a Caspase-Independent Pathway Promote Programmed Cell Death in Parallel to the Canonical Pathway for Apoptosis in Caenorhabditis elegans", "type"=>"journal", "authors"=>[{"first_name"=>"Daniel P.", "last_name"=>"Denning", "scopus_author_id"=>"57200593639"}, {"first_name"=>"Victoria", "last_name"=>"Hatch", "scopus_author_id"=>"6603440317"}, {"first_name"=>"H. Robert", "last_name"=>"Horvitz", "scopus_author_id"=>"7007006983"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "pui"=>"368694431", "sgr"=>"84876003933", "doi"=>"10.1371/journal.pgen.1003341", "scopus"=>"2-s2.0-84876003933", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"23505386"}, "id"=>"6d040da2-0c75-3686-b262-f68a719cf48d", "abstract"=>"Caspases are cysteine proteases that can drive apoptosis in metazoans and have critical functions in the elimination of cells during development, the maintenance of tissue homeostasis, and responses to cellular damage. Although a growing body of research suggests that programmed cell death can occur in the absence of caspases, mammalian studies of caspase-independent apoptosis are confounded by the existence of at least seven caspase homologs that can function redundantly to promote cell death. Caspase-independent programmed cell death is also thought to occur in the invertebrate nematode Caenorhabditis elegans. The C. elegans genome contains four caspase genes (ced-3, csp-1, csp-2, and csp-3), of which only ced-3 has been demonstrated to promote apoptosis. Here, we show that CSP-1 is a pro-apoptotic caspase that promotes programmed cell death in a subset of cells fated to die during C. elegans embryogenesis. csp-1 is expressed robustly in late pachytene nuclei of the germline and is required maternally for its role in embryonic programmed cell deaths. Unlike CED-3, CSP-1 is not regulated by the APAF-1 homolog CED-4 or the BCL-2 homolog CED-9, revealing that csp-1 functions independently of the canonical genetic pathway for apoptosis. Previously we demonstrated that embryos lacking all four caspases can eliminate cells through an extrusion mechanism and that these cells are apoptotic. Extruded cells differ from cells that normally undergo programmed cell death not only by being extruded but also by not being engulfed by neighboring cells. In this study, we identify in csp-3; csp-1; csp-2 ced-3 quadruple mutants apoptotic cell corpses that fully resemble wild-type cell corpses: these caspase-deficient cell corpses are morphologically apoptotic, are not extruded, and are internalized by engulfing cells. We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation.", "link"=>"http://www.mendeley.com/research/both-caspase-csp1-caspaseindependent-pathway-promote-programmed-cell-death-parallel-canonical-pathwa", "reader_count"=>40, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>30, "Physics and Astronomy"=>1, "Chemistry"=>1, "Computer Science"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "France"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/979800"], "description"=>"<p>(A) Representations of the intron-exon organization of the three known <i>csp-1</i> mRNA isoforms (<i>A</i>, <i>B</i> and <i>C</i>). Red bars indicate the <i>csp-1</i> deletion alleles used in this study; arrowheads indicate the SACRG sequence that encodes the caspase active-site. The graphic was generated using the Intron-Exon Graphic Maker (N. Bhatla; <a href=\"http://www.wormweb.org\" target=\"_blank\">www.wormweb.org</a>). (B) Extrachromosomal arrays carrying a wild-type genomic fragment of the <i>csp-1</i> locus or a mutant version that expresses only the <i>B</i> or <i>C</i> isoforms can rescue the <i>csp-1(n4967)</i> mutant phenotype. The <i>csp-1 PD</i>-only transgene contains two nonsense mutations that encode early stop codons affecting the <i>B</i> and <i>C</i> mRNA isoforms; the <i>csp-1A</i>-only transgene contains a mutation that changes the <i>B</i>/<i>C</i> start codon to an alanine codon; and the <i>csp-1B/C</i>-only transgene contains two nonsense mutations that encode early stop codons affecting the <i>A</i> isoform. The <i>csp-1</i> transgenes were injected into <i>csp-1(n4967); ced-3(n2436)</i> animals, and the resulting independent lines were assayed for <i>csp-1</i> rescuing activity by counting the number of extra undead cells in the anterior pharynx. The transgenes and their constructions are described in detail in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003341#s4\" target=\"_blank\">Materials and Methods</a>, and the complete data for each transgenic line are provided in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003341#pgen.1003341.s003\" target=\"_blank\">Table S2</a>. (C) RNAi knockdown of <i>csp-1</i> phenocopies the <i>csp-1</i> mutations. dsRNAs targeting the <i>csp-1</i> pro-domain or the <i>csp-1B</i> isoform were <i>in vitro</i> transcribed and injected into the gonads of RNAi-sensitive <i>rrf-3(pk1426); ced-3(n2436)</i> adult hermaphrodites. Progeny of the injected adults were assayed for extra undead cells in the anterior pharynx. PD, prodomain.</p>", "links"=>[], "tags"=>["isoforms", "programmed"], "article_id"=>646385, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_B_and_or_C_isoforms_of_csp_1_promote_programmed_cell_death_/646385", "title"=>"The B and/or C isoforms of <i>csp-1</i> promote programmed cell death.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-08 08:34:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/979804"], "description"=>"<p>(A) Fluorescence image of a transgenic <i>nIs290[</i>P<i><sub>mec-3</sub>::gfp]</i> larva expressing GFP from the <i>mec-3</i> promoter in the touch neurons (AVM, ALMs, PVM and PLMs, yellow arrows). <i>mec-3</i> is also expressed in the FLP and PVD neurons (white arrowheads). (B) Fluorescence image of a transgenic <i>nIs309[</i>P<i><sub>mec-7</sub>::csp-1B</i>, P<i><sub>mec-3</sub>::gfp]</i> larva expressing CSP-1B from the <i>mec-7</i> promoter (which is expressed in the AVM, ALM, PVM and PLM neurons) and GFP from the <i>mec-3</i> promoter. Note the absence of touch neurons. (C) Nomarski differential interference contrast (DIC) image of a refractile PLM cell corpse (arrow) in a <i>ced-1(e1735); ced-4(n1162); nIs309</i> L1 larva. (D) Transmission electron microscopic image of the cell corpse in (C). “n”, nucleus of the cell corpse; scale bar, 0.5 microns.</p>", "links"=>[], "tags"=>["overexpression", "ectopic"], "article_id"=>646389, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_csp_1B_overexpression_induces_ectopic_cell_deaths_/646389", "title"=>"<i>csp-1B</i> overexpression induces ectopic cell deaths.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-08 08:34:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/979808"], "description"=>"<p>(A–D) The percentages of PLM cells that survive in strains carrying P<i><sub>mec-7</sub>::ced-3</i>, P<i><sub>mec-7</sub>::csp-1B</i> or P<i><sub>mec-7</sub>::ced-4</i> transgenes. (A) <i>ced-9</i> protects against <i>ced-3</i>- but not <i>csp-1B</i>-cell-killing transgenes. (B) The cell-killing activity of <i>csp-1B</i> transgenes is mostly independent of <i>ced-3</i> and <i>ced-4</i>. The cell-killing activities of (C) <i>ced-3</i> and (D) <i>ced-4</i> transgenes do not require <i>csp-1</i>. PLM survival was scored based on the presence of GFP expressed from the <i>mec-3</i> promoter. Asterisks indicate <i>p</i><0.05 in a Fisher's exact test. All strains in (A) contained <i>ced-3(n3692)</i>. (E) A model depicting the genetic pathways regulating the caspase genes <i>csp-1</i> and <i>ced-3</i> (see text).</p>", "links"=>[], "tags"=>["cell-killing", "regulated", "canonical", "programmed"], "article_id"=>646393, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_csp_1B_cell_killing_activity_is_not_regulated_by_the_canonical_programmed_cell_death_pathway_/646393", "title"=>"<i>csp-1B</i> cell-killing activity is not regulated by the canonical programmed cell death pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-08 08:35:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/979822"], "description"=>"<p>Fluorescence <i>in situ</i> hybridization images of gonad arms of (A) an L4 hermaphrodite and (B) an adult hermaphrodite hybridized with Cy5-labelled probes complementary to <i>csp-1B</i>. The Cy5-labelled probes are visible as green puncta; the gonads are outlined in white. A schematic representation is shown above each micrograph. (C) Fluorescence <i>in situ</i> hybridization images of an adult hermaphrodite gonad hybridized with ALEXA594-labelled probes (red puncta) complementary to the region of <i>csp-1A</i> that encodes the prodomain (<i>csp-1A</i>) and Cy5-labelled <i>csp-1B</i> probes (green puncta) that hybridize to all <i>csp-1</i> transcript isoforms (total <i>csp-1</i>). White arrowheads indicate <i>csp-1A</i>-specific puncta; orange arrows indicate <i>csp-1B</i>-specific puncta, which are recognized strongly by the total <i>csp-1</i> probes but only weakly by the <i>csp-1A</i>-specific probes. (D) The number of CED-1::GFP-positive apoptotic cells in the gonads of caspase mutants exposed to 0 Gy and 120 Gy of ionizing radiation at the L4 larval stage. The strains were scored at 24 hrs and 48 hrs post L4-stage. Error bars indicate standard deviations.</p>", "links"=>[], "tags"=>["pachytene", "cells", "l4", "hermaphrodite"], "article_id"=>646406, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_csp_1_is_expressed_in_late_pachytene_cells_of_the_L4_and_adult_hermaphrodite_germline_/646406", "title"=>"<i>csp-1</i> is expressed in late pachytene cells of the L4 and adult hermaphrodite germline.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-08 08:37:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/979829"], "description"=>"<p>(A) Nomarski DIC and fluorescence images of a cell corpse within the head of a <i>ced-1(e1735); csp-1(n4967); csp-2(n4871) ced-3(n3692)</i> L1 larva carrying the integrated transgene <i>nIs342[</i>P<i><sub>egl-1</sub>::gfp]</i>, a transcriptional reporter that expresses GFP under the control of the BH3 domain-only encoding gene <i>egl-1</i>. (B) Nomarski DIC and fluorescence images of a cell corpse within the head of a <i>ced-1(e1735); csp-1(n4967); csp-2(n4871) ced-3(n3692)</i> L1 larva carrying the extrachromosomal array <i>nEx1646[</i>P<i><sub>dyn-1</sub>::mfg-e8::Venus]</i>, a fusion protein that binds to cell-surface exposed phosphatidylserine. (C) Representative transmission electron micrographs of cell corpses from <i>ced-1(e1735); csp-1(n4967); csp-2(n4871) ced-3(n3692)</i> larvae 24 hrs post hatching. “n”, nuclei of the cell corpses; scale bars, 0.5 microns. Note the difference in chromatin condensation between the two cell corpses.</p>", "links"=>[], "tags"=>["corpses", "caspase-deleted", "mutants", "cytologically", "morphologically"], "article_id"=>646413, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_cell_corpses_of_caspase_deleted_mutants_are_cytologically_and_morphologically_apoptotic_/646413", "title"=>"The cell corpses of caspase-deleted mutants are cytologically and morphologically apoptotic.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-08 08:38:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/979831"], "description"=>"<p>(A) Nomarski DIC and fluorescence images of a cell corpse from a <i>ced-1(e1735); csp-1(n4967); csp-2(n4871) ced-3(n3692)</i> L1 larva carrying the integrated transgene <i>nIs400[</i>P<i><sub>ced-1</sub>::ced-1ΔC::gfp]</i>, which expresses a non-rescuing CED-1ΔC::GFP fusion protein. CED-1 is a transmembrane receptor that is expressed on engulfing cells, binds to apoptotic cell corpses, and is required for phagocytosis <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003341#pgen.1003341-Zhou1\" target=\"_blank\">[46]</a>. (B) Nomarski DIC and fluorescence images of a cell corpse from a <i>csp-3(n4872); csp-1(n4967); csp-2(n4871) ced-3(n3692)</i> L1 larva stained with acridine orange (AO), which fluoresces in engulfed cell corpses undergoing degradation in endosomal compartments. (C) The fraction of <i>csp-1(n4967); csp-2(n4871) ced-3(n3692)</i> and <i>ced-1(e1735); csp-1(n4967); csp-2(n4871) ced-3(n3692)</i> with 0, 1, 2 or >2 cell corpses at different time points post hatching. Asterisks indicate p<0.05 in a Mann-Whitney test comparing the two genotypes at a given time point.</p>", "links"=>[], "tags"=>["corpses", "engulfed"], "article_id"=>646415, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Caspase_independent_cell_corpses_are_engulfed_and_degraded_/646415", "title"=>"Caspase-independent cell corpses are engulfed and degraded.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-08 08:39:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/979834", "https://ndownloader.figshare.com/files/979835", "https://ndownloader.figshare.com/files/979837", "https://ndownloader.figshare.com/files/979839", "https://ndownloader.figshare.com/files/979843", "https://ndownloader.figshare.com/files/979845", "https://ndownloader.figshare.com/files/979848"], "description"=>"<div><p>Caspases are cysteine proteases that can drive apoptosis in metazoans and have critical functions in the elimination of cells during development, the maintenance of tissue homeostasis, and responses to cellular damage. Although a growing body of research suggests that programmed cell death can occur in the absence of caspases, mammalian studies of caspase-independent apoptosis are confounded by the existence of at least seven caspase homologs that can function redundantly to promote cell death. Caspase-independent programmed cell death is also thought to occur in the invertebrate nematode <i>Caenorhabditis elegans</i>. The <i>C. elegans</i> genome contains four caspase genes (<i>ced-3</i>, <i>csp-1</i>, <i>csp-2</i>, and <i>csp-3</i>), of which only <i>ced-3</i> has been demonstrated to promote apoptosis. Here, we show that CSP-1 is a pro-apoptotic caspase that promotes programmed cell death in a subset of cells fated to die during <i>C. elegans</i> embryogenesis. <i>csp-1</i> is expressed robustly in late pachytene nuclei of the germline and is required maternally for its role in embryonic programmed cell deaths. Unlike CED-3, CSP-1 is not regulated by the APAF-1 homolog CED-4 or the BCL-2 homolog CED-9, revealing that <i>csp-1</i> functions independently of the canonical genetic pathway for apoptosis. Previously we demonstrated that embryos lacking all four caspases can eliminate cells through an extrusion mechanism and that these cells are apoptotic. Extruded cells differ from cells that normally undergo programmed cell death not only by being extruded but also by not being engulfed by neighboring cells. In this study, we identify in <i>csp-3; csp-1; csp-2 ced-3</i> quadruple mutants apoptotic cell corpses that fully resemble wild-type cell corpses: these caspase-deficient cell corpses are morphologically apoptotic, are not extruded, and are internalized by engulfing cells. We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation.</p> </div>", "links"=>[], "tags"=>["caspase", "csp-1", "caspase-independent", "pathway", "programmed", "parallel", "canonical", "apoptosis"], "article_id"=>646418, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.s001", "https://dx.doi.org/10.1371/journal.pgen.1003341.s002", "https://dx.doi.org/10.1371/journal.pgen.1003341.s003", "https://dx.doi.org/10.1371/journal.pgen.1003341.s004", "https://dx.doi.org/10.1371/journal.pgen.1003341.s005", "https://dx.doi.org/10.1371/journal.pgen.1003341.s006", "https://dx.doi.org/10.1371/journal.pgen.1003341.s007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Both_the_Caspase_CSP_1_and_a_Caspase_Independent_Pathway_Promote_Programmed_Cell_Death_in_Parallel_to_the_Canonical_Pathway_for_Apoptosis_in_Caenorhabditis_elegans__/646418", "title"=>"Both the Caspase CSP-1 and a Caspase-Independent Pathway Promote Programmed Cell Death in Parallel to the Canonical Pathway for Apoptosis in <em>Caenorhabditis elegans</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-08 08:39:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/1006420"], "description"=>"<p>The number of refractile cell corpses per head was counted in L1 larvae within one hour of hatching.</p>", "links"=>[], "tags"=>["deaths", "caspase"], "article_id"=>667044, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_deaths_occur_in_the_absence_of_all_C_elegans_caspase_genes_/667044", "title"=>"Cell deaths occur in the absence of all <i>C. elegans</i> caspase genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-07 01:57:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1006434"], "description"=>"1<p>Homozygous for the integrated transgene <i>nIs106[P<sub>lin-11</sub>::gfp]</i>.</p>2<p>Includes animals that were either homozygous for <i>unc-75(+)</i> or <i>unc-75(e950)</i>.</p>3<p>Homozygous for <i>dpy-20(e1282ts)</i>.</p><p>For the statistical comparisons between <i>ced-3(n2427)</i> or <i>ced-3(n2436)</i> and double mutants with each <i>csp</i> allele, <i>p</i> values were considered significant if less than 0.01 to correct for multiple comparisons.</p>", "links"=>[], "tags"=>["caspase", "homolog", "programmed", "anterior"], "article_id"=>667061, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_caspase_homolog_csp_1_promotes_programmed_cell_death_in_the_C_elegans_anterior_pharynx_/667061", "title"=>"The caspase homolog <i>csp-1</i> promotes programmed cell death in the <i>C. elegans</i> anterior pharynx.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-07 01:57:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1006455"], "description"=>"<p><i>n</i>, number of animals assayed; for each animal, six touch neurons (AVM, ALML, ALMR, PVM, PLML and PLMR) were scored for survival using the P<i><sub>mec-3</sub>::gfp</i> reporter transgene.</p>*<p>Each strain contained the transgene P<i><sub>mec-3</sub>::gfp</i>, which expressed GFP in the FLP, AVM, ALM, PVM, PVD and PLM neurons.</p>", "links"=>[], "tags"=>["promoter", "requires", "conserved", "cysteine", "putative", "caspase"], "article_id"=>667077, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ectopic_expression_of_csp_1B_from_the_mec_7_promoter_can_kill_touch_neurons_and_this_killing_activity_requires_the_conserved_cysteine_in_the_putative_caspase_active_site_/667077", "title"=>"Ectopic expression of <i>csp-1B</i> from the <i>mec-7</i> promoter can kill touch neurons, and this killing activity requires the conserved cysteine in the putative caspase active site.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-07 01:57:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1006473"], "description"=>"a<p>Heterozygous for <i>unc-30(e191)/+</i>.</p>b<p>Heterozygous for <i>unc-75(e950)/+</i>.</p>", "links"=>[], "tags"=>["maternally", "programmed", "deaths", "embryonically", "presumptive", "anterior"], "article_id"=>667099, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Daniel P. Denning", "Victoria Hatch", "H. Robert Horvitz"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003341.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_csp_1_is_maternally_required_for_programmed_cell_deaths_that_occur_embryonically_in_the_presumptive_anterior_pharynx_/667099", "title"=>"<i>csp-1</i> is maternally required for programmed cell deaths that occur embryonically in the presumptive anterior pharynx.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-07 01:58:19"}

PMC Usage Stats | Further Information

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Relative Metric

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