Dally Proteoglycan Mediates the Autonomous and Nonautonomous Effects on Tissue Growth Caused by Activation of the PI3K and TOR Pathways
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{"title"=>"Dally proteoglycan mediates the autonomous and nonautonomous effects on tissue growth caused by activation of the PI3K and TOR pathways", "type"=>"journal", "authors"=>[{"first_name"=>"Ana", "last_name"=>"Ferreira", "scopus_author_id"=>"57192838753"}, {"first_name"=>"Marco", "last_name"=>"Milán", "scopus_author_id"=>"7006489639"}], "year"=>2015, "source"=>"PLoS Biology", "identifiers"=>{"pmid"=>"26313758", "doi"=>"10.1371/journal.pbio.1002239", "sgr"=>"84940661124", "scopus"=>"2-s2.0-84940661124", "issn"=>"15457885", "pui"=>"605833427"}, "id"=>"9d6732af-c15a-34e1-8cfd-b2b5cc57a791", "abstract"=>"How cells acquiring mutations in tumor suppressor genes outcompete neighboring wild-type cells is poorly understood. The phosphatidylinositol 3-kinase (PI3K)-phosphatase with tensin homology (PTEN) and tuberous sclerosis complex (TSC)-target of rapamycin (TOR) pathways are frequently activated in human cancer, and this activation is often causative of tumorigenesis. We utilized the Gal4-UAS system in Drosophila imaginal primordia, highly proliferative and growing tissues, to analyze the impact of restricted activation of these pathways on neighboring wild-type cell populations. Activation of these pathways leads to an autonomous induction of tissue overgrowth and to a remarkable nonautonomous reduction in growth and proliferation rates of adjacent cell populations. This nonautonomous response occurs independently of where these pathways are activated, is functional all throughout development, takes place across compartments, and is distinct from cell competition. The observed autonomous and nonautonomous effects on tissue growth rely on the up-regulation of the proteoglycan Dally, a major element involved in modulating the spreading, stability, and activity of the growth promoting Decapentaplegic (Dpp)/transforming growth factor β(TGF-β) signaling molecule. Our findings indicate that a reduction in the amount of available growth factors contributes to the outcompetition of wild-type cells by overgrowing cell populations. During normal development, the PI3K/PTEN and TSC/TOR pathways play a major role in sensing nutrient availability and modulating the final size of any developing organ. We present evidence that Dally also contributes to integrating nutrient sensing and organ scaling, the fitting of pattern to size.", "link"=>"http://www.mendeley.com/research/dally-proteoglycan-mediates-autonomous-nonautonomous-effects-tissue-growth-caused-activation-pi3k-to", "reader_count"=>33, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>14, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>6, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>14, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>6, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>14, "Agricultural and Biological Sciences"=>14, "Medicine and Dentistry"=>3, "Neuroscience"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}}, "reader_count_by_country"=>{"Spain"=>2}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2230081"], "description"=>"<p>(A) <i>ci>GFP</i>, <i>ci>Rheb</i>, and <i>ci>Dp110</i> wing imaginal discs labelled with TUNEL to visualize apoptotic cells (in red or white). The <i>ci</i> domain is labelled with GFP (in green), and the boundary between A and P cells is marked by a red line. (B) Histogram plotting the quantification of the absolute number of TUNEL-positive cells in the A (light green bars) and P (grey bars) compartments of the indicated genotypes. Error bars indicate the standard deviation. Number of wing discs analyzed per genotype ≥ 10. ***<i>p</i> < 0.001. (C, D) Cuticle preparations of <i>en>GFP</i>, <i>Rheb</i> (C), and <i>ci>GFP</i>, <i>Dp110</i> (D) adult wings either in a wild-type background, in a heterozygous background for <i>H99</i> (a deficiency that uncovers <i>reaper</i>, <i>hid</i>, and <i>grim</i> proapoptotic genes), or coexpressing a dominant negative form of Dp53 (Dp53<sup>Ct</sup>). The blue line marks the boundary between the A and P compartments. The domains of transgene expression are marked with a blue asterisk. (C’, D’, E) Histograms plotting tissue size (C’, D’, E) and cell density values (C’, E) of the transgene-expressing compartment (blue bars) and the adjacent cell populations (white bars) of adult wings with the indicated genotypes normalized as a percent of the control wings. Error bars show the standard deviation. Number of wings analyzed per genotype ≥ 10. ***<i>p</i> < 0.001; **<i>p</i> < 0.01; *<i>p</i> < 0.05. (F) Cuticle preparations of <i>ci>GFP</i> adult wings of well-fed (100 g/L yeast food, top) and starved (20 g/L yeast food, bottom) animals. Note the reduction in wing size caused by starvation. (G, H) Histograms plotting tissue size of the transgene-expressing compartment (blue bars) and the adjacent cell populations (white bars) of adult wings with the indicated genotypes normalized as a percent of the control wings. Error bars show the standard deviation. Number of wings analyzed per genotype ≥ 10. ***<i>p</i> < 0.001; **<i>p</i> < 0.01; *<i>p</i> < 0.05. Quantification was made in well-fed (100 g/L yeast food, left histogram) and starved (20 g/L yeast food, right histogram) animals of identical genotypes.</p>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525147, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002239.g003", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_nonautonomous_reduction_in_tissue_size_upon_targeted_activation_of_the_PI3K_PTEN_and_TSC_TOR_pathways_does_not_rely_on_Dp53_activity_and_apoptosis_and_is_not_affected_by_nutrient_restriction_/1525147", "title"=>"The nonautonomous reduction in tissue size upon targeted activation of the PI3K/PTEN and TSC/TOR pathways does not rely on Dp53 activity and apoptosis and is not affected by nutrient restriction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-27 02:44:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/2230112", "https://ndownloader.figshare.com/files/2230113", "https://ndownloader.figshare.com/files/2230114", "https://ndownloader.figshare.com/files/2230115", "https://ndownloader.figshare.com/files/2230117"], "description"=>"<div><p>How cells acquiring mutations in tumor suppressor genes outcompete neighboring wild-type cells is poorly understood. The phosphatidylinositol 3-kinase (PI3K)–phosphatase with tensin homology (PTEN) and tuberous sclerosis complex (TSC)-target of rapamycin (TOR) pathways are frequently activated in human cancer, and this activation is often causative of tumorigenesis. We utilized the Gal4-UAS system in <i>Drosophila</i> imaginal primordia, highly proliferative and growing tissues, to analyze the impact of restricted activation of these pathways on neighboring wild-type cell populations. Activation of these pathways leads to an autonomous induction of tissue overgrowth and to a remarkable nonautonomous reduction in growth and proliferation rates of adjacent cell populations. This nonautonomous response occurs independently of where these pathways are activated, is functional all throughout development, takes place across compartments, and is distinct from cell competition. The observed autonomous and nonautonomous effects on tissue growth rely on the up-regulation of the proteoglycan Dally, a major element involved in modulating the spreading, stability, and activity of the growth promoting Decapentaplegic (Dpp)/transforming growth factor β(TGF-β) signaling molecule. Our findings indicate that a reduction in the amount of available growth factors contributes to the outcompetition of wild-type cells by overgrowing cell populations. During normal development, the PI3K/PTEN and TSC/TOR pathways play a major role in sensing nutrient availability and modulating the final size of any developing organ. We present evidence that Dally also contributes to integrating nutrient sensing and organ scaling, the fitting of pattern to size.</p></div>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525173, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1002239.s001", "https://dx.doi.org/10.1371/journal.pbio.1002239.s002", "https://dx.doi.org/10.1371/journal.pbio.1002239.s003", "https://dx.doi.org/10.1371/journal.pbio.1002239.s004", "https://dx.doi.org/10.1371/journal.pbio.1002239.s005"], "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dally_Proteoglycan_Mediates_the_Autonomous_and_Nonautonomous_Effects_on_Tissue_Growth_Caused_by_Activation_of_the_PI3K_and_TOR_Pathways_/1525173", "title"=>"Dally Proteoglycan Mediates the Autonomous and Nonautonomous Effects on Tissue Growth Caused by Activation of the PI3K and TOR Pathways", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-08-27 02:44:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/2230092"], "description"=>"<p>(A–E) Cuticle preparations of adult wings expressing the indicated transgenes under the control of the <i>ci-gal4</i> (A, C) or <i>en-gal4</i> (B, D, E) drivers. The blue line marks the boundary between the anterior (A) and posterior (P) compartments, and the domains of transgene expression are marked with a blue asterisk. On the right side of each panel, histograms plotting tissue size (A–E) and cell density (A–D) of the transgene-expressing (blue bars) or nonexpressing (white bars) compartments of adult wings expressing the indicated transgenes. Error bars show the standard deviation. Number of wings analyzed per genotype ≥ 10. ***<i>p</i> < 0.001; ** <i>p</i> < 0.01; *<i>p</i> < 0.05.</p>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525158, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002239.g006", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dally_contributes_to_the_autonomous_and_nonautonomous_effects_of_targeted_deregulation_of_the_PI3K_PTEN_TSC_TOR_and_hippo_yorkie_pathways_/1525158", "title"=>"Dally contributes to the autonomous and nonautonomous effects of targeted deregulation of the PI3K/PTEN, TSC/TOR, and hippo/yorkie pathways.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-27 02:44:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/2230089"], "description"=>"<p>(A, B) Representative wing discs of the indicated genotypes labeled to visualize <i>dally-lacZ</i> (antibody to β-Gal, green or white) and myrTomato (myrT, in red) expression to mark the transgene-expressing domain. Note stronger expression of <i>dally-lacZ</i> upon activation of the PI3K/PTEN, TSC/TOR, or hippo/Yorkie pathways (red brackets). (C, E) Cuticle preparations of male adult wings overexpressing Dally under the control of the <i>ci-gal4</i> (C) or <i>en-gal4</i> (E) drivers. The blue line marks the boundary between the anterior (A) and posterior (P) compartments, and the domains of Dally overexpression are marked with a blue asterisk. (D, F). Histograms plotting tissue size (left) and cell density values (right) of the Dally-expressing domains (blue bars) and the adjacent compartments (white bars) of adult wings overexpressing Dally under the control of the <i>ci-gal4</i> (D) or <i>en-gal4</i> (F) drivers. Values are normalized as a percent of the control (GFP-expressing) wings. Error bars show the standard deviation. Number of wings analyzed per genotype ≥ 10. ***<i>p</i> < 0.001; **<i>p</i> < 0.01. (G, H) Histograms plotting the size of clones (in a.u., G) and the number of cells per clone (H) located in the A or P compartment of <i>ci-gal4</i>, <i>UAS-GFP</i> and <i>ci-gal4</i>, <i>UAS-GFP/UAS-Dally</i> wing discs. Clones were generated at the beginning of the third instar period and quantified 72 h later in late third instar wing discs. Error bars indicate the standard deviation. Number of clones analyzed per genotype ≥ 30. ***<i>p</i> < 0.001. Size of clones (A compartment, a.u.): ci>GFP = 388 ± 141; ci>GFP, Dally = 537 ± 169. Size of clones (P compartment, a.u.): ci>GFP = 348 ± 140; ci>GFP, Dally = 182 ± 89. Number of cells per clone (A compartment): ci>GFP = 20 ± 7; ci>GFP, Dally = 28 ± 12. Number of cells per clone (P compartment): ci>GFP = 23 ± 7; ci>GFP, Dally = 10 ± 4. (I) Wing imaginal discs of <i>ci>GFP</i> and <i>ci>GFP</i>, <i>Dally</i> larvae labelled to visualize pMAD protein (in red or white) and GFP (in green). (J) Average pMAD profiles of wing discs expressing <i>GFP</i> (red line) or <i>GFP</i> and <i>Dally</i> (blue line) under the control of the <i>ci-gal4</i> driver. Profiles were taken along the AP axis and plotted in absolute positions. The standard error to the mean is shown in the corresponding color for each genotype. The AP boundary of both experiments was aligned to allow comparison of the profile in each compartment. Number of wing discs analyzed per genotype ≥ 5. (K) Histogram plotting the total intensity of the pMAD signal in a.u. of the anterior (blue bars) and posterior (white bars) compartments of <i>ci>GFP</i> and <i>ci>Dally</i>, <i>GFP</i> wing discs. Error bars indicate the standard deviation. Number of wing discs analyzed per genotype ≥ 5. ***<i>p</i> < 0.001; **<i>p</i> < 0.01.</p>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525155, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002239.g005", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overexpression_of_Dally_phenocopies_the_autonomous_and_nonautonomous_effects_of_targeted_activation_of_the_PI3K_PTEN_and_TSC_TOR_pathways_/1525155", "title"=>"Overexpression of Dally phenocopies the autonomous and nonautonomous effects of targeted activation of the PI3K/PTEN and TSC/TOR pathways.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-27 02:44:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/2230097"], "description"=>"<p>(A) Activation of the PI3K/PTEN, TSC/TOR, or Yorkie pathways in a defined cell population (in blue) increases cell and/or tissue size in an autonomous manner and induces a nonautonomous reduction in both cell size and number in neighboring cell populations (in grey). Whereas the autonomous and nonautonomous effects on tissue size are mediated by Dally, the effects on cell size are Dally independent. The nonautonomous reduction in tissue size is a consequence of reduced Dpp signaling, most probably reflecting increased number of Dpp molecules bound to the overgrowing (Dally overexpressing) tissue and a consequent reduction in the number of available Dpp molecules to the neighboring cell population. (B) Within the feeding animal, the PI3K/PTEN and TSC/TOR pathways sense nutrient conditions and modulate both cell and tissue size. Whereas the effects on tissue size are mediated by the glypican Dally, which modulates the spreading of the Dpp morphogen throughout the tissue, the effects on cell size are Dally independent.</p>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525163, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002239.g008", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_role_of_Dally_in_tissue_growth_/1525163", "title"=>"A role of Dally in tissue growth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-27 02:44:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/2230079"], "description"=>"<p>(A) Quantification of tissue size (in arbitrary units [a.u.]) of both anterior (A) and posterior (P) domains of wing imaginal discs of the indicated genotypes in three distinct time points during development (in hours [h] AEL). Error bars show the standard deviation. Number of wing discs analyzed per genotype ≥ 15. ***<i>p</i> < 0.001; **<i>p</i> < 0.01. (B) Examples of <i>ci>GFP</i> (upper panel) and <i>ci>GFP</i>, <i>Dp110</i> (lower panel) wing imaginal discs in the developmental time points shown in panel A. The transgene-expressing domain is marked with GFP (in green), and the disc is labelled with DAPI (in blue). The A and P compartments are indicated. (C, D) Histograms plotting the size of clones (in a.u., C) and the number of cells per clone (D) located in the A or P compartment of <i>ci-gal4</i>,<i>UAS-GFP</i> and <i>ci-gal4</i>, <i>UAS-GFP/UAS-Dp110</i> wing discs. Clones were generated at the beginning of the third instar period and quantified 72 h later in late third instar wing discs. Error bars indicate the standard deviation. Number of clones analyzed per genotype ≥ 30. ***<i>p</i> < 0.001. Size of clones (A compartment, a.u.): ci>GFP = 388 ± 141; ci>GFP, Dp110 = 587 ± 249. Size of clones (P compartment, a.u.): ci>GFP = 348 ± 140; ci>GFP, Dp110 = 114 ± 67. Number of cells per clone (A compartment): ci>GFP = 20 ± 7; ci>GFP, Dp110 = 23 ± 8. Number of cells per clone (P compartment): ci>GFP = 23 ± 7; ci>GFP, Dp110 = 9 ± 4. (E) Examples of clones of cells in <i>ci>GFP</i> (left panel) and <i>ci>GFP</i>, <i>Dp110</i> (right panel) wing discs and induced in the developmental time points shown in C and D. The transgene-expressing domain is marked with GFP (in green), and the clones are labeled by the absence of nuclear red fluorescent protein (RFP, red) expression. The A and P compartments are indicated.</p>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525145, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002239.g002", "stats"=>{"downloads"=>3, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Targeted_activation_of_the_PI3K_PTEN_and_TSC_TOR_pathways_induces_a_nonautonomous_reduction_in_growth_rates_in_adjacent_cell_populations_/1525145", "title"=>"Targeted activation of the PI3K/PTEN and TSC/TOR pathways induces a nonautonomous reduction in growth rates in adjacent cell populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-27 02:44:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/2230096"], "description"=>"<p>(A–D) Cuticle preparations (A, C) and histograms plotting tissue size normalized as a percent of the control wings (B, D) of <i>nub>Rheb</i> (A, B) or <i>nub>Dp110</i> (C, D) adult wings coexpressing either <i>GFP</i> or <i>dally</i><sup><i>RNAi</i></sup>. Two independent RNA interference (RNAi) lines were used in B. Error bars show the standard deviation. Number of wings analyzed per genotype ≥ 10. ***<i>p</i> < 0.001. (E) Representative wing discs of the indicated genotypes labeled to visualize <i>dally-lacZ</i> (antibody to β-Gal, green or white) and myrT expression (in red) to mark the transgene-expressing domain. Higher magnification pictures of the squared regions are shown on the right side. Note the reduced expression of <i>dally-lacZ</i> upon depletion of the TSC/TOR or PTEN/PI3K pathways. (F) Representative wing discs of the indicated genotypes and labeled to visualize Ci (red) and DAPI (in blue). Ci labels the anterior compartment. A, anterior compartment; P, posterior compartment. (G) Histogram plotting the P/A size ratio of wing discs of the indicated genotypes. Error bars show the standard deviation. Number of wing discs analyzed per genotype ≥ 10. ***<i>p</i> < 0.001. P/A ratios: hh>2XGFP = 0.55 ± 0.02; hh>GFP, Dp110-RNAi = 0.29 ± 0.06; hh>dally, Dp110-RNAi = 0.42 ± 0.07. (H) Histogram plotting absolute size in a.u. of adult wings of the indicated genotypes. Quantification was made in well-fed (100 g/L yeast food) and starved (20 g/L yeast food) animals. Error bars show the standard deviation. Number of wings analyzed per genotype ≥ 10. ***<i>p</i> < 0.001. ns, not significant.</p>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525162, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002239.g007", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dally_acts_as_a_bridge_between_nutrient_sensing_and_wing_scaling_/1525162", "title"=>"Dally acts as a bridge between nutrient sensing and wing scaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-27 02:44:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/2230076"], "description"=>"<p>(A, E, I) Schemes of adult wings with the <i>nub</i> (A), <i>ci</i> (E), and <i>en</i> (I) expression domains marked in blue and cuticle preparations of male adult wings expressing <i>GFP</i> or <i>PTEN</i><sup><i>RNAi</i></sup> under the control of the <i>nub-gal4</i> (A), <i>ci-gal4</i> (E), and <i>en-gal4</i> (I) drivers. The blue line marks the boundary between anterior (A) and posterior (P) compartments. The wing is decorated with four longitudinal veins (L2–L5), and the anterior side of L4 corresponds to the AP compartment boundary. (B–D, F–H, J–L) Histograms plotting tissue size (B, C, F, G, J, K) and cell density (D, H, L) of the whole wing (B, F, J), or the A and P compartments of adult wings expressing the indicated transgenes in the <i>nub</i> (B–D), <i>ci</i> (F–H) or <i>en</i> (J–L) domains normalized as a percent of the control wings. Note a consistent reduction in tissue size of the adjacent cell populations in G and K (white bars). (M) Cuticle preparation of a <i>ci>stg</i>, <i>cycE</i> adult wing. The blue line marks the boundary between the A and P compartments. On the right are histograms plotting tissue size and cell density values of the A (blue bars) and P (white bars) domains of <i>ci>stg</i>, <i>cycE</i> adult wings normalized as a percent of the control (<i>ci>GFP</i>) wings. <i>ci-gal4</i> drives gene expression to the A compartment of the wing. (N) Cuticle preparations of <i>spalt</i><sup><i>PE</i></sup><i>>GFP</i> and <i>spalt</i><sup><i>PE</i></sup><i>>PTEN</i><sup><i>RNAi</i></sup> adult wings. The blue lines mark the lateral and medial regions of the wing. On the right are histograms plotting tissue size and cell density values of the medial (blue bars) and lateral (white bars) regions of <i>spalt</i><sup><i>PE</i></sup><i>>PTEN</i><sup><i>RNAi</i></sup> adult wings normalized as a percent of the control (<i>spalt</i><sup><i>PE</i></sup><i>>GFP</i>) wings. <i>spalt-gal4</i> drives gene expression to the medial part of the wing. The domains of transgene expression in A, E, I, M, and N are marked with a blue asterisk. Error bars show the standard deviation. Number of wings analyzed per genotype ≥ 10. ***<i>p</i> < 0.001; **<i>p</i> < 0.01; *<i>p</i> < 0.05. Area and cell density values of the cell populations driving transgene expression are labeled in blue, and the values of the nonexpressing domain are represented in white.</p>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525142, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002239.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nonautonomous_effects_on_tissue_size_upon_targeted_activation_of_PI3K_PTEN_and_TSC_TOR_pathways_/1525142", "title"=>"Nonautonomous effects on tissue size upon targeted activation of PI3K/PTEN and TSC/TOR pathways.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-27 02:44:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/2230087"], "description"=>"<p>(A) Cuticle preparation of adult wings expressing <i>GFP</i> or <i>Dp110</i> under the control of the <i>ci-gal4</i> driver, which drives transgene expression in the anterior compartment. Note the expansion of the anterior intervein regions (blue arrows) upon induction of growth and the corresponding reduction of the posterior intervein regions (grey arrows). The anterior (A) and posterior (P) compartments are labeled, and the AP boundary is marked by a red line. (B) Wing imaginal disc of <i>ci>GFP</i> and <i>ci>PTEN</i><sup><i>RNAi</i></sup> larvae labelled to visualized Ci protein (in green) and β-galactosidase (βGal) (in red or white) to visualize <i>dpp</i> (dpp-lacZ) expression. The width of the <i>dpp-lacZ</i> stripe (normalized with respect to the width of the wing pouch) was <i>ci>GFP</i> = 0.082 ± 0.005; <i>ci>PTEN</i><sup><i>RNAi</i></sup> = 0.088 ± 0.003; <i>p</i> = 0.55; <i>n</i> > 6. (C) Wing imaginal discs of <i>ci>GFP</i> and <i>ci>GFP</i>, <i>Dp110</i> larva labelled to visualize Spalt (in red) and GFP (in green) protein expression. The white dashed line marks the boundary between A and P cells. The lower panels show magnification of the Spalt domain. Note that the anterior Spalt domain is wider upon Dp110 expression (thick bracket) whereas the posterior Spalt domain (thin brackets) gets reduced. (D) Wing imaginal discs of <i>ci>GFP</i> and <i>ci>GFP</i>, <i>Dp110</i> larva labelled to visualize pMAD protein (in red or white) and GFP (in green). Lower panels show magnifications of the pMAD domains, and the red line marks the boundary between the A and P compartments. Horizontal yellow lines were used to generate the pMAD profiles shown in E–I. (E, F, H, I) Average pMAD profiles of wing discs expressing <i>GFP</i> (red line) or <i>GFP</i> and the corresponding transgenes (blue line) under the control of the <i>ci-gal4</i> driver. Profiles were taken along the AP axis and plotted in absolute positions. The standard error to the mean is shown in the corresponding color for each genotype. In E, the AP boundary of each experiment is marked by a dashed line of the corresponding color. In F, the AP boundary of both experiments was aligned to allow comparison of the profile in each compartment. Number of wing discs analyzed per genotype ≥ 5. The domains of transgene expression are marked with a black asterisk. Arrows mark the limits of the Dpp activity gradients. (G, J) Histograms plotting the total intensity of the pMAD signal in a.u. of the anterior (blue bars) and posterior (white bars) compartments of <i>ci>GFP</i> (G, J) and <i>ci>Dp110</i> (G) or <i>ci>Rheb</i> (J) wing discs. Error bars indicate the standard deviation. Number of wing discs analyzed per genotype ≥ 5. ***<i>p</i> < 0.001. (K) Wing imaginal discs of <i>nub>GFP</i> and <i>nub>Dp110</i> larvae labelled to visualize pMAD protein (in red), GFP (in green), and DAPI (in blue, to visualize nuclei). (L) Average pMAD profile of wing discs expressing <i>GFP</i> (red line) or <i>Dp110</i> (blue line) in the <i>nubbin</i> domain. Profiles were taken along the AP axis and plotted in absolute positions. The standard error to the mean is shown in the corresponding color for each genotype. Number of wing discs analyzed per genotype ≥ 7. (M) Histogram plotting the total intensity of the pMAD signal in a.u. of the <i>nubbin</i> domain of <i>nub>GFP</i> (red bar) and <i>nub>Dp110</i> (blue bar) discs. Error bars indicate the standard deviation. Number of wing discs analyzed per genotype ≥ 5. (N) Histogram plotting the area (in a.u.) of anterior (blue) and posterior (white) domains of wing discs expressing <i>GFP</i> or <i>GFP</i> and <i>Dp110</i> in the <i>ci</i> domain. Error bars show the standard deviation. Number of wing discs analyzed per genotype ≥ 15. ***<i>p</i> < 0.001 (O) Histogram plotting the area (in a.u.) of anterior (blue) and posterior (white) domains of wing discs expressing either <i>GFP</i> or <i>Dp110</i> in the <i>ci</i> domain together with a dsRNA form against <i>dpp</i>. Error bars show the standard deviation. Number of wing discs analyzed per genotype ≥ 15. ***<i>p</i> < 0.001, **<i>p</i> < 0.01. (P) Wing imaginal discs of <i>ci>GFP</i> and <i>ci>dpp</i><sup><i>RNAi</i></sup> larvae labelled to visualize GFP (in green) and DAPI (in blue, to visualize nuclei).</p>", "links"=>[], "tags"=>["pten", "tsc", "Drosophila imaginal primordia", "nonautonomou", "tumor suppressor genes outcompete", "overgrowing cell populations", "PI 3K", "tor", "tissue", "tgf", "pathway", "Dally Proteoglycan Mediates"], "article_id"=>1525153, "categories"=>["Uncategorised"], "users"=>["Ana Ferreira", "Marco Milán"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1002239.g004", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Autonomous_and_nonautonomous_effects_on_Dpp_activity_levels_upon_targeted_activation_of_the_PI3K_PTEN_and_TSC_TOR_pathways_/1525153", "title"=>"Autonomous and nonautonomous effects on Dpp activity levels upon targeted activation of the PI3K/PTEN and TSC/TOR pathways.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-27 02:44:55"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}

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