Topography of Thalamic Projections Requires Attractive and Repulsive Functions of Netrin-1 in the Ventral Telencephalon
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{"title"=>"Topography of thalamic projections requires attractive and repulsive functions of netrin-1 in the ventral telencephalon", "type"=>"journal", "authors"=>[{"first_name"=>"Ashton W.", "last_name"=>"Powell", "scopus_author_id"=>"16242406800"}, {"first_name"=>"Takayuki", "last_name"=>"Sassa", "scopus_author_id"=>"7007024709"}, {"first_name"=>"Yongqin", "last_name"=>"Wu", "scopus_author_id"=>"24328161100"}, {"first_name"=>"Marc", "last_name"=>"Tessier-Lavigne", "scopus_author_id"=>"7006342144"}, {"first_name"=>"Franck", "last_name"=>"Polleux", "scopus_author_id"=>"6603365364"}], "year"=>2008, "source"=>"PLoS Biology", "identifiers"=>{"pui"=>"351824741", "issn"=>"15449173", "isbn"=>"1545-7885 (Electronic) 1544-9173 (Linking)", "doi"=>"10.1371/journal.pbio.0060116", "scopus"=>"2-s2.0-45149083168", "pmid"=>"18479186", "sgr"=>"45149083168"}, "id"=>"7b74303f-ab03-3699-a524-f8383697a714", "abstract"=>"Recent studies have demonstrated that the topography of thalamocortical (TC) axon projections is initiated before they reach the cortex, in the ventral telencephalon (VTel). However, at this point, the molecular mechanisms patterning the topography of TC projections in the VTel remains poorly understood. Here, we show that a long-range, high-rostral to low-caudal gradient of Netrin-1 in the VTel is required in vivo for the topographic sorting of TC axons to distinct cortical domains. We demonstrate that Netrin-1 is a chemoattractant for rostral thalamic axons but functions as a chemorepulsive cue for caudal thalamic axons. In accordance with this model, DCC is expressed in a high-rostromedial to low-caudolateral gradient in the dorsal thalamus (DTh), whereas three Unc5 receptors (Unc5A-C) show graded expression in the reverse orientation. Finally, we show that DCC is required for the attraction of rostromedial thalamic axons to the Netrin-1-rich, anterior part of the VTel, whereas DCC and Unc5A/C receptors are required for the repulsion of caudolateral TC axons from the same Netrin-1-rich region of the VTel. Our results demonstrate that a long-range gradient of Netrin-1 acts as a counteracting force from ephrin-A5 to control the topography of TC projections before they enter the cortex.", "link"=>"http://www.mendeley.com/research/topography-thalamic-projections-requires-attractive-repulsive-functions-netrin1-ventral-telencephalo", "reader_count"=>70, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>7, "Student > Doctoral Student"=>2, "Researcher"=>18, "Student > Ph. D. Student"=>20, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>4, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>9}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>7, "Student > Doctoral Student"=>2, "Researcher"=>18, "Student > Ph. D. Student"=>20, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>4, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>9}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>44, "Medicine and Dentistry"=>6, "Neuroscience"=>12, "Arts and Humanities"=>1, "Physics and Astronomy"=>1, "Psychology"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>12}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>44}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>11, "China"=>1, "Brazil"=>1, "France"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>5}

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  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"3"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/931990"], "description"=>"<div><p>(A and E) Schema of the experimental paradigm: rostral (DTR; [A–D]) or caudal (DTC; [E–H]) thalamic explants isolated from β-actin::EGFP E14.5 embryos were cocultured with E14.5 whole-mount telencephalon from either wild-type isochronic embryos (B and F) or <i>Netrin-1</i> knockout isochronic embryos (C and G) in order to test for the requirement of Netrin-1 specifically in the VTel.</p>\n <p>(B and C) DTR axons show a strong preferential outgrowth in the rostral part of the wild-type VTel (green arrow in [B]). A contingent of wild-type DTR axons grow significantly more caudally in a Netrin-1–deficient VTel (red arrow in [C]), whereas another contingent of TC axons maintains its projection to the rostral part of the VTel (double arrowheads in [C]). L, lateral; R, rostral.</p>\n <p>(D) Quantification of normalized optical density (OD) of DTR-EGFP axons growing in wild-type (<i>n</i> = 13, green) or <i>Netrin-1</i> knockout (<i>n</i> = 7, red) telencephalon. Significantly more EGFP-positive axons are growing in the caudal part of the VTel in the <i>Netrin-1</i> knockout than in the wild-type telencephalon. Triple asterisks (***) indicate <i>p</i> < 0.001, ANOVA one-way test (bins vs. genotype).</p>\n <p>(F and G) Axons originating from the caudal DTh preferentially grow in the caudal part of wild-type VTel (green arrow in [F]) but grow significantly more rostrally in the Netrin-1–deficient VTel (red arrowhead in [G]).</p>\n <p>(H) Quantification of normalized optical density (OD) of DTC-EGFP axons growing in wild-type (<i>n</i> = 13, green) or <i>Netrin-1</i> knockout (<i>n</i> = 7, red) telencephalon. The raster-like dot plots presented under each histogram (D and H) represents the significance of individual bin comparisons between the two experimental conditions according to a Fisher PLSD post hoc test (a single dot [•] indicates <i>p</i> < 0.05; double dots [••] indicate <i>p</i> < 0.01; and triple dots [•••] indicate <i>p</i> < 0.001).</p>\n <p>Scale bars in (B, C, F, and G) represent 300 μm.</p></div>", "links"=>[], "tags"=>["ventral", "telencephalon", "topography", "rostral", "caudal", "thalamic"], "article_id"=>602432, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g005", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Netrin_1_Is_Required_in_the_Ventral_Telencephalon_to_Specify_the_Topography_of_Projection_of_Both_Rostral_and_Caudal_Thalamic_Axons_/602432", "title"=>"Netrin-1 Is Required in the Ventral Telencephalon to Specify the Topography of Projection of Both Rostral and Caudal Thalamic Axons", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:40:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/932439"], "description"=>"<div><p>(A and C–K) At E14.5, mRNA in situ hybridization (ISH) for <i>Gbx2</i> delineates the DTh along its rostrocaudal axis on horizontal sections distributed along the doesoventral axis of the DTh ([C, F, and I]; see levels of section in [A]).</p>\n <p>Expression of <i>bHLHB4</i> on adjacent sections delineates the pretectum (PT) (D, G, and J). When merged (E, F, and K), <i>Gbx2</i> and <i>bHLHB4</i> show nonoverlapping and complementary expression at the diencephalic–mesencephalic boundary delineating the caudal limit of the DTh (DT) on E14.5 horizontal sections.</p>\n <p>(B and L–W) In situ hybridization for <i>DCC</i> ([L, O, R, and U], green in [N, Q, T, and W]), <i>Unc5A</i> ([M], red in [N]), <i>Unc5B</i> ([P], red in [Q]), and <i>Unc5C</i> ([S and V], red in [T and W]) on adjacent horizontal sections of E14.5 mouse embryos isolated at two levels of sections along the dorsoventral axis of the DTh (B). <i>DCC</i> is expressed most highly in a rostromedial domain of the DTh in postmitotic regions (unpublished data) and is excluded from the thin ventricular zone left at this time (bracket in [L]). Conversely, <i>Unc5A</i>, <i>Unc5B</i>, and <i>Unc5C</i> are all expressed in nonoverlapping caudolateral domains of the DTh (stars in [N, Q, T, and W] indicate the approximate peak of expression). The dashed lines in (N, Q, T, and W) correspond to the actual limit of the DTh as defined by <i>Gbx2</i> expression on adjacent sections (see [I–K]). Note that <i>DCC</i> is expressed at low, but significant, levels in the caudolateral domain of the DTh (red arrows in [U]) where it is coexpressed with <i>Unc5C</i> (star in [V]).</p>\n <p>(X and Y) Quantification of the gradient of <i>DCC</i> (<i>n</i> = 10), <i>Unc5A</i> (<i>n</i> = 5), <i>Unc5B</i> (<i>n</i> = 4), and <i>Unc5C</i> (<i>n</i> = 6 sections) mRNA expression along the rostrocaudal axis (X) and the mediolateral axis (Y) of the DTh at E14.5 as indicated by the lines in (L). Gradients were measured by normalizing the optical density values on multiple adjacent sections (number indicated in [Y]) shown in (L–W).</p>\n <p>Arrowheads in (L, O, R, and U) indicate the midline.</p></div>", "links"=>[], "tags"=>["netrin-1", "receptors", "dorsal"], "article_id"=>602881, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g007", "stats"=>{"downloads"=>2, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patterns_of_Expression_of_Netrin_1_Receptors_in_the_Mouse_Dorsal_Thalamus_/602881", "title"=>"Patterns of Expression of Netrin-1 Receptors in the Mouse Dorsal Thalamus", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:48:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/932706"], "description"=>"<p>(A and E) Isochronic whole-mount telencephalic cocultures with EGFP-expressing rostral (B–D) or caudal (F–H) DTh explants were incubated either with control isotype mouse IgG (B and F) or function-blocking anti-Unc5A/C polyclonal antibody (Ab) (C and G). Blocking the function of Unc5A/C receptors does not affect the rostral outgrowth of DTR axons (see [C and D]) but induces a significantly more-rostral outgrowth of DTC axons in the VTel (see [G and H]). Quantification of normalized optical density (OD) of DTR-EGFP axons (D) or DTC-EGFP axons (H) growing in VTel with function-blocking anti-Unc5A/C antibodies (red curves) or control mouse anti-IgG antibodies (green curves). NS, nonsignificant (<i>p</i> > 0.05); triple asterisks (***) indicate <i>p</i> < 0.001, ANOVA one-way test (overall effect: bins versus experimental conditions). For comparisons, the gray curves represent the distribution of control DTR axons (in [D]) and control DTC axons (in [H]) cultured without antibody as shown in <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-g005\" target=\"_blank\">Figure 5</a>D and <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-g005\" target=\"_blank\">5</a>H. The raster-like dot plot presented under each histogram represents the significance of individual bin comparisons performed between the two experimental conditions using a PLSD-post-hoc test (a single dot [•] indicates <i>p</i> < 0.05; double dots [••] indicate <i>p</i> < 0.01; and triple dots [•••] indicate <i>p</i> < 0.001). L, lateral; R, rostral.</p>", "links"=>[], "tags"=>["receptors", "repulsion", "caudal", "dt", "axons", "rostral", "ventral"], "article_id"=>603141, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g009", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Unc5A_and_C_Receptors_Are_Required_for_the_Repulsion_of_Caudal_DT_Axons_from_the_Netrin_1_8211_Rich_Rostral_Domain_of_the_Ventral_Telencephalon_/603141", "title"=>"Unc5A and C Receptors Are Required for the Repulsion of Caudal DT Axons from the Netrin-1–Rich Rostral Domain of the Ventral Telencephalon", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:52:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/931770"], "description"=>"<div><p>(A) Diagram of the level of the oblique sections used to visualize TC projections in (B–G).</p>\n <p>(B–G) Injections of BDA in the rostral third of the DTh (DT) of control (wild-type <i>Netrin-1<sup>+/+</sup></i>; [B–D]) or <i>Netrin-1</i> knockout (<i>Netrin-1</i><sup>−/−</sup>) E18.5 embryos (E–G) reveal that thalamic axons originating from the rostral-most part of the DTh project more caudally (arrows in [F and G]) in the VTel of <i>Netrin-1</i> knockout than in control embryos.</p>\n <p>(H–O) Averaged axon density maps showing the distribution of thalamic axons at the CSB of E18.5 wild-type (green) or <i>Netrin-1</i><sup>−/−</sup> embryos (red) for thalamic injections clustered along the rostromedial axis ([I–K]; as depicted in [H]) or the mediolateral axis ([M–O]; as depicted in [L]).</p>\n <p>(P–S) Averaged density maps of injection sites in the DTh leading to thalamic axons crossing the CSB at the rostral- (Q), medial- (R), or caudal-most (S) third of the CSB in the wild-type control mice (green) or <i>Netrin-1</i><sup>−/−</sup> at E18.5. For statistical analysis of these density maps, see <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-sg006\" target=\"_blank\">Figure S6</a>.</p>\n <p>C, caudal; D, dorsal. R, rostral; V, ventral.</p></div>", "links"=>[], "tags"=>["topography", "thalamocortical", "projections", "ganglionic", "eminence"], "article_id"=>602214, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Netrin_1_Is_Necessary_for_the_Establishment_of_the_Topography_of_Thalamocortical_Projections_in_the_Ganglionic_Eminence_In_Vivo_/602214", "title"=>"Netrin-1 Is Necessary for the Establishment of the Topography of Thalamocortical Projections in the Ganglionic Eminence In Vivo", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:36:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/932950"], "description"=>"<div><p>Schemas summarizing previous [<a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-b011\" target=\"_blank\">11</a>] and present findings regarding the axon guidance cues controlling the topographic sorting of TC axons in the VTel.</p>\n <p>(A) High rostromedial and low caudolateral gradient of EphA receptors (EphA3-4-7) mediate chemopulsion of rostromedial DTh (DT) axons to the high-caudal to low-rostral gradient of ephrin-A5 in the VTel.</p>\n <p>(B and C). In the present study, we demonstrate that a high-rostral to low-caudal gradient of Netrin-1 in the VTel plays a critical role in the topographic projection of DTh axons in the VTel. We show that the rostromedial domain of the DTh expresses high levels of DCC and that the caudolateral domain of the DTh expresses low levels of DCC, which is required both for the attraction of DTR axons and the repulsion of DTC axons to the Netrin-1–rich rostral domain of the VTel. We also show that Unc5A and B are expressed preferentially in the caudolateral domain of the DT, and Unc5C is expressed in a high-caudolateral to low-rostromedial gradient in the DTh. Finally, we provide evidence that (1) Unc5A/C are required for the repulsion of caudal DTh axons from the Netrin-1–rich domain of the VTel, but (2) they do not play any significant role in the projection of rostromedial DTh axons, and (3) that overexpression of Unc5C in DTR axons is sufficient to convert their outgrowth into DTC outgrowth, i.e., repulsion away from the Netrin-1–rich rostral domain of the VTel.</p>\n <p>A1, primary auditory area; GE, ganglionic eminence; M1, primary motor area; S1, primary somatosensory area; V1, primary visual area.</p></div>", "links"=>[], "tags"=>["netrin-1", "topography", "thalamocortical", "projections", "ventral"], "article_id"=>603393, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g011", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_of_the_Role_of_Netrin_1_Signaling_in_the_Topography_of_Thalamocortical_Projections_in_the_Ventral_Telencephalon_/603393", "title"=>"Model of the Role of Netrin-1 Signaling in the Topography of Thalamocortical Projections in the Ventral Telencephalon", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:56:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/932301"], "description"=>"<div><p>(A and E) Experimental paradigm: control 293 cells (B and F) or 293 cells stably expressing Netrin-1 and embedded in collagen (C and G) were grafted in proximity of the caudal part of the VTel of E14.5 wild-type whole-mount telencephalon cocultured with EGFP-expressing explants isolated from isochronic rostral DTh (DTR; [B and C]) or caudal DTh (DTC; [F and G]).</p>\n <p>(B and C) Axons originating from the rostral DTh grow rostrally in the VTel of telencephalic whole mount grafted with control 293 cells in the caudal VTel (green arrow in [B]). In contrast, a significant proportion of DTR axons project caudally when Netrin-1–expressing cells are grafted in the caudal VTel (red arrows in [C]). L, lateral; R, rostral.</p>\n <p>(D) Quantification of normalized optical density (OD) of DTR-EGFP axons growing in VTel grafted caudally with control 293 cells (green) or VTel grafted caudally with Netrin-1–expressing 293 cells (red).</p>\n <p>(F and G) Axons originating from the caudal DTh grow caudally in the VTel of a telencephalic whole mount with control 293 cells grafted in the caudal VTel (green arrowheads in [F]). In contrast, a significant proportion of DTC axons grow rostrally when Netrin-1–expressing cells are grafted in the caudal VTel (red arrowhead in [G]).</p>\n <p>(H) Quantification of normalized optical density (OD) of DTC-EGFP axons growing in VTel with control 293 cells grafted caudally (green) or VTel with Netrin-1–expressing 293 cells grafted caudally (red). Significantly more DTC axons grow to the rostral part of the VTel grafted with Netrin-1–expressing cells than in control graft. Triple asterisks (***) indicate <i>p</i> < 0.001, ANOVA one-way test (overall effect: bins versus experimental conditions). The raster-like dot plot presented under each histogram (D and H) represents the significance of individual bins comparisons performed between the two experimental conditions according to a Fisher PLSD post hoc test (a single dot [•] indicates <i>p</i> < 0.05; double dots [••] indicate <i>p</i> < 0.01; and triple dots [•••] indicate <i>p</i> < 0.001).</p>\n <p>Scale bars in (B, C, F, and G) represent 150 μm.</p></div>", "links"=>[], "tags"=>["acting", "chemoattractive", "rostral", "thalamic", "axons", "chemorepulsive", "caudal"], "article_id"=>602728, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g006", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Netrin_1_Is_Acting_as_a_Chemoattractive_Cue_for_Rostral_Thalamic_Axons_and_a_Chemorepulsive_Cue_for_Caudal_Thalamic_Axons_/602728", "title"=>"Netrin-1 Is Acting as a Chemoattractive Cue for Rostral Thalamic Axons and a Chemorepulsive Cue for Caudal Thalamic Axons", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:45:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/932854"], "description"=>"<div><p>(A) Experimental approach: E14.5 250-μm–thick slices containing the rostral or caudal domain of the DTh were microinjected and electroporated using a control IRES-myristoylated (m)Venus or a Unc5C-IRES-mVenus expression plasmid. Immediately following electroporation, DTR or DTC explants were isolated and cocultured with a whole-mount telencephalon for 4 d in vitro (DIV). Following fixation and staining with anti-EGFP antibodies, individual DTR or DTC fluorescent axons or fascicles were traced and superimposed on a referenced-plot that was then quantified using ImageJ for optical density distribution in three radial bins. DIV, days in vitro; WT, wild type.</p>\n <p>(B–D) DTR (B) and DTC (D) axons electroporated with control mVenus-expression plasmid grow preferentially to the rostral and caudal domain of the VTel, respectively. However, DTR axons overexpressing Unc5C grow significantly more caudally than control DTR axons (B) in the VTel, suggesting that Unc5C expression is sufficient to convert DTR into the DTC pattern of axon growth in the VTel.</p>\n <p>(E) Quantification of the results shown in (B–D) analyzing the percentage of fluorescent axons located in caudal, medial, and rostral bins of the VTel</p>\n <p>Triple asterisks (***) indicate <i>p</i> < 0.001, ANOVA one-way test (overall effect: bins versus experimental conditions). NS, nonsignificant (<i>p</i> > 0.05); a single dot [•] indicates <i>p</i> < 0.05; and double dots [••] indicate <i>p</i> < 0.01: significance of individual bin comparisons performed between the two experimental conditions using a Fisher PLSD post hoc test.</p></div>", "links"=>[], "tags"=>["unc5c", "rostral", "dorsal", "thalamus", "induce", "repulsion", "dtr", "axons", "ventral"], "article_id"=>603281, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g010", "stats"=>{"downloads"=>2, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_Unc5C_in_the_Rostral_Part_of_the_Dorsal_Thalamus_Is_Sufficient_to_Induce_Repulsion_of_DTR_Axons_from_Netrin_1_8211_Rich_Rostral_Domain_of_the_Ventral_Telencephalon_/603281", "title"=>"Expression of Unc5C in the Rostral Part of the Dorsal Thalamus Is Sufficient to Induce Repulsion of DTR Axons from Netrin-1–Rich Rostral Domain of the Ventral Telencephalon", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:54:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/931885"], "description"=>"<div><p>(A) Rostral (red) or caudal (green) explants isolated from the mantle region of the ganglionic eminence (VTel) were isolated from 250-μm–thick vibratome sections and grafted into the caudal part of the VTel of a recipient E14.5 whole-mount telencephalic vesicle as described previously (Seibt et al., 2003 [<a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-b010\" target=\"_blank\">10</a>]). The rostral part of the DTh (DTR) isolated from coronal slices of an isochronic β-actin::EGFP-expressing mouse embryo (see <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-sg011\" target=\"_blank\">Figure S11</a> for details on explant isolation) is cocultured with the whole-mount telencephalon for 4 d in vitro (div; see <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#s4\" target=\"_blank\">Materials and Methods</a> for details). CGE, caudal ganglionic eminence; GE, ganglionic eminence; LGE, lateral ganglionic eminence; MGE, medial ganglionic eminence; WT, wild type.</p>\n <p>(B) Homotopic grafting (caudal VTel into caudal VTel) results in a normal outgrowth of rostral thalamic axons into the rostral domain of the VTel (arrow). L, lateral; R, rostral.</p>\n <p>(C) In contrast, heterotopic grafting (rostral VTel into the caudal VTel) results in a pronounced change in the topography of DTR axon projections, which invade more-caudal territories (red arrows) than in control grafts (see [B]).</p>\n <p>(D) Quantification of the topography of rostral thalamic axon outgrowth in the VTel presenting homotopic (green) or heterotopic (red) VTel graft into the caudal VTel. The gray curve illustrates the topography of DTR axons projection in control, nongrafted, experiments shown in <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-g005\" target=\"_blank\">Figure 5</a>D. Each histogram represents the average normalized optical density (OD) from the EGFP signal measured in 60 radial bins centered on the thalamic explant as shown in (D′). Triple asterisks (***) indicate <i>p</i> < 0.001, ANOVA one-way test (overall effect: bins versus experimental conditions). The raster-like dot plot presented under the histograms represents the significance of individual bin comparisons between the two experimental conditions according to a Fisher Protected Least Significant Difference (PLSD) post hoc test (a single dot [•] indicates <i>p</i> < 0.05; and double dots [••] indicate <i>p</i> < 0.01).</p>\n <p>Scale bars in (B and C) represent 250 μm.</p></div>", "links"=>[], "tags"=>["rostral", "ganglionic", "eminence", "contains", "chemoattractant", "thalamic"], "article_id"=>602322, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g002", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Rostral_Part_of_the_Ganglionic_Eminence_Contains_a_Chemoattractant_for_Rostral_Thalamic_Axons_/602322", "title"=>"The Rostral Part of the Ganglionic Eminence Contains a Chemoattractant for Rostral Thalamic Axons", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:38:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/459543", "https://ndownloader.figshare.com/files/459596", "https://ndownloader.figshare.com/files/459638", "https://ndownloader.figshare.com/files/459664", "https://ndownloader.figshare.com/files/459690", "https://ndownloader.figshare.com/files/459742", "https://ndownloader.figshare.com/files/459784", "https://ndownloader.figshare.com/files/459817", "https://ndownloader.figshare.com/files/459852", "https://ndownloader.figshare.com/files/459875", "https://ndownloader.figshare.com/files/459906", "https://ndownloader.figshare.com/files/459928"], "description"=>"<div><p>Recent studies have demonstrated that the topography of thalamocortical (TC) axon projections is initiated before they reach the cortex, in the ventral telencephalon (VTel). However, at this point, the molecular mechanisms patterning the topography of TC projections in the VTel remains poorly understood. Here, we show that a long-range, high-rostral to low-caudal gradient of Netrin-1 in the VTel is required in vivo for the topographic sorting of TC axons to distinct cortical domains. We demonstrate that Netrin-1 is a chemoattractant for rostral thalamic axons but functions as a chemorepulsive cue for caudal thalamic axons. In accordance with this model, <em>DCC</em> is expressed in a high-rostromedial to low-caudolateral gradient in the dorsal thalamus (DTh), whereas three <em>Unc5</em> receptors (<em>Unc5A–C</em>) show graded expression in the reverse orientation. Finally, we show that DCC is required for the attraction of rostromedial thalamic axons to the Netrin-1–rich, anterior part of the VTel, whereas DCC and Unc5A/C receptors are required for the repulsion of caudolateral TC axons from the same Netrin-1–rich region of the VTel. Our results demonstrate that a long-range gradient of Netrin-1 acts as a counteracting force from ephrin-A5 to control the topography of TC projections before they enter the cortex.</p> </div>", "links"=>[], "tags"=>["topography", "thalamic", "projections", "requires", "repulsive", "functions", "netrin-1", "ventral", "telencephalon"], "article_id"=>150547, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.0060116.sg001", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg002", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg003", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg004", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg005", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg006", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg007", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg008", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg009", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg010", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg011", "https://dx.doi.org/10.1371/journal.pbio.0060116.sg012"], "stats"=>{"downloads"=>11, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Topography_of_Thalamic_Projections_Requires_Attractive_and_Repulsive_Functions_of_Netrin_1_in_the_Ventral_Telencephalon/150547", "title"=>"Topography of Thalamic Projections Requires Attractive and Repulsive Functions of Netrin-1 in the Ventral Telencephalon", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-05-13 00:09:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/931635"], "description"=>"<div><p>(A) Averaged axon density maps quantified from multiple BDA injections (<i>n</i> numbers in [A1–A3]) clustered in three, arbitrarily defined thirds along the rostrocaudal axis of the E18.5 mouse DTh (red indicates rostral; green, medial; and blue, caudal; as shown in [A′]). (A1–A3) Individual average axon density maps for thalamic injections clustered in the rostral- (A1), medial- (A2), or caudal-most (A3) third of the DTh.</p>\n <p>(B) Averaged axon density maps quantified from multiple BDA injections clustered along the mediolateral axis of the DTh (red indicates medial; green, central; and blue, lateral; as shown in [B′]).</p>\n <p>(C) Averaged axon density maps shown in (A1) (rostral-most third of DT split in lateral and medial halves), (A2) (medial third along rostrocaudal extent), and (A3) (caudal third along rostrocaudal extent) were further subdivided into halves (C1) or thirds (C2 and C3) along the mediolateral axis. This analysis demonstrates the topographic segregation of thalamic axon projections before they enter the cortex at E18.5.</p>\n <p>(D and D′) Averaged position of BDA injection sites in the DTh leading to axons crossing CSB at its rostral- (red), medial- (green), or caudal-most (blue) third. This 2-D map represents a dorsal view of the DTh, compressed along its dorsoventral axis.</p>\n <p>(D1–D3) Individual averaged density maps of thalamic injection sites leading to axons crossing the CSB at its rostral- (D1), medial- (D2), or caudal-most (D3) third.</p>\n <p>(E) Schematic representation of the anatomical location of our 2-D, averaged axon density maps shown in this figure as well as <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-g004\" target=\"_blank\">Figures 4</a>, <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-sg003\" target=\"_blank\">S3</a>, and <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-sg005\" target=\"_blank\">S5</a>.</p>\n <p>C, caudal; D, dorsal; R, rostral; V, ventral.</p></div>", "links"=>[], "tags"=>["topography", "thalamocortical", "projections", "achieved", "ventral", "telencephalon", "entering"], "article_id"=>602069, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Precise_Topography_of_Thalamocortical_Projections_Achieved_at_the_Level_of_the_Ventral_Telencephalon_Before_Entering_the_Cortex_/602069", "title"=>"Precise Topography of Thalamocortical Projections Achieved at the Level of the Ventral Telencephalon Before Entering the Cortex", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:34:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/932557"], "description"=>"<div><p>(A and E) Isochronic whole-mount telencephalic cocultures with EGFP-expressing rostral (B–D) or caudal (F–H) DTh explants were incubated either with control isotype mouse IgG (B and F) or function-blocking anti-DCC monoclonal antibody (mAb) (C and G). Blocking DCC receptor function randomizes the outgrowth of both rostral and caudal DTh axons. L, lateral; R, rostral.</p>\n <p>(M) Quantification of normalized optical density (OD) of DTR-EGFP axons (D) or DTC-EGFP axons (H) growing in VTel with function-blocking anti-DCC antibodies (red curves) or control mouse anti-IgG antibodies (green curves). Triple asterisks (***) indicate <i>p</i> < 0.001, ANOVA one-way test (overall effect: bins versus experimental conditions). For comparisons, the gray curves represent the distribution of control DTR axons (in [D]) and control DTC axons (in [H]) cultured without antibody as shown in <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-g005\" target=\"_blank\">Figure 5</a>D and <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060116#pbio-0060116-g005\" target=\"_blank\">5</a>H. The raster-like dot plot presented under each histogram represents the significance of individual bin comparisons performed between the two experimental conditions using a Fisher PLSD post hoc test (a single dot [•] indicates <i>p</i> < 0.05; double dots [••] indicate <i>p</i> < 0.01; and triple dots [•••] indicate <i>p</i> < 0.001).</p></div>", "links"=>[], "tags"=>["rostral", "thalamic", "axons", "repulsion", "caudal", "ventral"], "article_id"=>602998, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g008", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DCC_Is_Required_for_Both_Attraction_of_Rostral_Thalamic_Axons_and_Repulsion_of_Caudal_Thalamic_Axons_from_the_Netrin_1_8211_Rich_Rostral_Domain_of_the_Ventral_Telencephalon_/602998", "title"=>"DCC Is Required for Both Attraction of Rostral Thalamic Axons and Repulsion of Caudal Thalamic Axons from the Netrin-1–Rich Rostral Domain of the Ventral Telencephalon", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/932153"], "description"=>"<div><p>(A–D) mRNA in situ hybridization performed on horizontal sections of E14.5 (A and B) and E15.5 (C and D) mouse embryos reveals that <i>Netrin-1</i> mRNA is expressed in a high-rostral to low-caudal gradient in the VTel. Also note that Netrin-1 is expressed in the DTh itself (arrowheads in [A] and [C]). (B) shows a higher magnification of the red boxed area in (A); (D) shows a higher magnification of the green boxed area in (C).</p>\n <p>(E) Series of 18 coronal sections from a single E15.5 wild-type mouse brain showing that the high-rostral to low-caudal gradient of <i>Netrin-1</i> mRNA expression is found in the mantle region of the ganglionic eminence. Sections are numbered from rostral (#1) to caudal (#18). Arrowheads indicate the location of the internal capsule.</p>\n <p>(F and G) This rostrocaudal gradient can also be visualized on horizontal sections of a <i>Netrin-1<sup>LacZ/+</sup></i> E15.5 mouse embryo both at low (F) and high (G) magnification on horizontal sections immunostained for β-galactosidase.</p>\n <p>(H) This high-rostral to low-caudal gradient of Netrin-1 expression coincides spatially with TC axons in the internal capsule in the VTel as visualized by this double immunofluorescence for the cell adhesion molecule L1 (green) and β-galactosidase (red).</p>\n <p>(I) Quantification of the gradient of <i>Netrin-1</i> mRNA expression inside the VTel at E14.5 (red), E15.5 (green), and β-galactosidase immunofluorescence in a <i>Netrin-1<sup>LacZ/+</sup></i> E15.5 mouse (blue) using normalized optical density measurement in 30 vertical bins oriented along the rostrocaudal axis on horizontal sections. <i>n</i> indicates the number of sections used to measure the normalized optical density values along the rostrocaudal axis. In (B, D, and G), arrowheads point to the rostrocaudal and dorsoventral width of the internal capsule within the VTel.</p>\n <p>Scale bars represent in (A) 800 μm; (B) 250 μm; (C) 1 mm; (D) 250 μm; (E) 80 μm; (F) 600 μm; and (G and H) 200 μm.</p></div>", "links"=>[], "tags"=>["high-rostral", "low-caudal", "gradient", "ganglionic"], "article_id"=>602591, "categories"=>["Neuroscience"], "users"=>["Ashton W Powell", "Takayuki Sassa", "Yongqin Wu", "Marc Tessier-Lavigne", "Franck Polleux"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.0060116.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Netrin_1_Is_Expressed_in_a_High_Rostral_to_Low_Caudal_Gradient_in_the_Ganglionic_Eminence_/602591", "title"=>"Netrin-1 Is Expressed in a High-Rostral to Low-Caudal Gradient in the Ganglionic Eminence", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-05-13 00:43:11"}

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Relative Metric

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