Wnt5a Regulates Midbrain Dopaminergic Axon Growth and Guidance
Publication Date
March 31, 2011
Journal
PLOS ONE
Authors
Brette D. Blakely, Christopher R. Bye, Chathurini V. Fernando, Malcolm K. Horne, et al
Volume
6
Issue
3
Pages
e18373
DOI
https://dx.plos.org/10.1371/journal.pone.0018373
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0018373
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/21483795
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069098
Europe PMC
http://europepmc.org/abstract/MED/21483795
Web of Science
000289057200066
Scopus
79953651370
Mendeley
http://www.mendeley.com/research/wnt5a-regulates-midbrain-dopaminergic-axon-growth-guidance
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Mendeley | Further Information

{"title"=>"Wnt5a regulates midbrain dopaminergic axon growth and guidance", "type"=>"journal", "authors"=>[{"first_name"=>"Brette D.", "last_name"=>"Blakely", "scopus_author_id"=>"47161051100"}, {"first_name"=>"Christopher R.", "last_name"=>"Bye", "scopus_author_id"=>"23481436100"}, {"first_name"=>"Chathurini V.", "last_name"=>"Fernando", "scopus_author_id"=>"8578792400"}, {"first_name"=>"Malcolm K.", "last_name"=>"Horne", "scopus_author_id"=>"35502711100"}, {"first_name"=>"Maria L.", "last_name"=>"Macheda", "scopus_author_id"=>"6506199075"}, {"first_name"=>"Steven A.", "last_name"=>"Stacker", "scopus_author_id"=>"35444491800"}, {"first_name"=>"Ernest", "last_name"=>"Arenas", "scopus_author_id"=>"7005858454"}, {"first_name"=>"Clare L.", "last_name"=>"Parish", "scopus_author_id"=>"8966004000"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-79953651370", "doi"=>"10.1371/journal.pone.0018373", "sgr"=>"79953651370", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "pmid"=>"21483795", "issn"=>"19326203", "pui"=>"361550129"}, "id"=>"c22b0a60-95e5-330f-a8f6-94534f9317ab", "abstract"=>"During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway). Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB) as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.", "link"=>"http://www.mendeley.com/research/wnt5a-regulates-midbrain-dopaminergic-axon-growth-guidance", "reader_count"=>65, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>5, "Researcher"=>4, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>2, "Other"=>4, "Student > Master"=>9, "Student > Bachelor"=>6, "Lecturer"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>5, "Researcher"=>4, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>2, "Other"=>4, "Student > Master"=>9, "Student > Bachelor"=>6, "Lecturer"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>46, "Medicine and Dentistry"=>4, "Neuroscience"=>6}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>46}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Argentina"=>1, "Netherlands"=>1, "United States"=>1, "United Kingdom"=>1, "Australia"=>1}, "group_count"=>4}

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/787497"], "description"=>"<p>(<b>A</b>) Schematic representation of the explant cultures. VM\n explants were plated in collagen adjacent to mock- or Wnt5a-transfected\n cell aggregates. After three days in culture, the number of DA neurites\n (TH<sup>+</sup>) radiating from the proximal and distal sides\n of the VM explant (relative to the aggregate) were counted and expressed\n as a ratio. (<b>B</b>) In co-cultures of E11.5 mouse VM explants\n with Wnt5a-transfected cells, the majority of TH<sup>+</sup>\n neurites emanated from the distal side of the explant, an effect that\n could be ablated by bath application of casein kinase 1 inhibitor D4476,\n Rac1 inhibitor NSC23766 and anti-Fz3-CRD. (<b>C</b>) The ability\n of Wnt5a to induce repulsion of DA neurites was maintained in older\n cultures (E14.5 mouse explants). Photomicrographs of E11.5 VM explants\n co-cultured with (<b>D</b>) mock-transfected cell aggregates and\n (<b>E</b>) Wnt5a-transfected cell aggregates. (<b>F</b>)\n VM explant co-cultured with Wnt5a cell aggregate, illustrating the\n specificity of Wnt5a to repel TH<sup>+</sup> fibers\n (<b>F</b>) but not total neurite fibers (<b>F</b>',\n TUJ1-labeled fibers). (<b>G</b>–<b>I</b>) Images\n illustrating the effects of Wnt5a on neurite chemotaxis could be ablated\n by (<b>G</b>) D4476, (<b>H</b>) NSC23766 and\n (<b>I</b>) anti-Fz3-CRD. Dashed line demarcates the border of the\n cell aggregate. Arrow indicates direction of ligand signal (i.e. cell\n aggregate) relative to explant. Scale bar  = 200\n µm.</p>", "links"=>[], "tags"=>["acts", "chemorepellant", "da", "neurites", "vm"], "article_id"=>457856, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018373.g006", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Wnt5a_acts_as_a_chemorepellant_for_DA_neurites_in_VM____explants_/457856", "title"=>"Wnt5a acts as a chemorepellant for DA neurites in VM\n explants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-03-31 02:10:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/394128", "https://ndownloader.figshare.com/files/394178", "https://ndownloader.figshare.com/files/394200"], "description"=>"<div><p>During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, <em>Wnt5a</em> is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway). Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in <em>Wnt5a</em><sup>−/−</sup> mice, where fasciculation of the medial forebrain bundle (MFB) as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.</p> </div>", "links"=>[], "tags"=>["wnt5a", "regulates", "midbrain", "dopaminergic", "axon", "and"], "article_id"=>137836, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0018373.s001", "https://dx.doi.org/10.1371/journal.pone.0018373.s002", "https://dx.doi.org/10.1371/journal.pone.0018373.s003"], "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Wnt5a_Regulates_Midbrain_Dopaminergic_Axon_Growth_and___Guidance/137836", "title"=>"Wnt5a Regulates Midbrain Dopaminergic Axon Growth and\n Guidance", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-03-31 02:10:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/786635"], "description"=>"<p>(<b>A</b>) In situ hybridization in a coronal section of the mouse\n midbrain showed Wnt5a expression overlapping with (<b>B</b>)\n TH<sup>+</sup> cells in the developing ventral midbrain at\n E11.5, during the period of initiation of neurite outgrowth.\n (<b>C</b>) Merged image of TH and Wnt5 expression.\n (<b>D</b>) Sagittal section of mouse VM at E11.5 illustrating\n TH<sup>+</sup> fibers polarized towards the DM, as indicated by\n the arrows. (<b>E</b>) Sagittal section at E11.5 revealed a high\n rostral to low caudal gradient of Wnt5a in the VM, (<b>F</b>)\n surrounding the DA neurons and neurites as well as higher expression at\n the ventricular zone compared to the mantle zone. (<b>G</b>)\n Merged image of TH and Wnt5 expression depicted in E and F.\n (<b>H</b>) At E14.5, during maturation of the midbrain\n dopamine pathways, a coronal section revealed Wnt5a expression was\n maintained in the VM, overlapping with (<b>I</b>) the\n TH<sup>+</sup> cells. (<b>J</b>) Merged image of TH and\n Wnt5 expression. (<b>K</b>) Photomicrograph illustrating DA fibers\n in the MFB approaching the LGE at E14.5.\n (<b>L</b>–<b>N</b>) Sagittal section (medial to\n panel (<b>K</b>)) illustrating reversal of the Wnt5a gradient,\n with Wnt5a expression greater in the caudal VM than rostral VM.\n (<b>M</b>') Enlargement from (<b>M</b>)\n illustrating dorsal trajectory of TH<sup>+</sup> fibers\n (<b>N</b>') Enlargement from (<b>N</b>)\n illustrating that Wnt5a is most likely secreted from\n TH<sup>−</sup> cells. Filled arrow-head: Wnt5a-labeled cell\n (red). Unfilled arrow-head: TH<sup>+</sup> neuron (green).\n (<b>O</b>) Dissected VM from TH-GFP mice were analyzed by flow\n cytometry and sorted into GFP<sup>+</sup> (TH<sup>+</sup>\n neurons) and GFP<sup>−</sup> (non-DA neurons). Q-PCR revealed that\n the majority of Wnt5a expression was not in the DA neurons\n (TH-GFP<sup>-</sup> fraction). Scale bars:\n A–C,E–G,H–J,L–N = 100\n µm; D,N' = 25 µm. Data represents\n mean ± s.e.m., n = 5, * p<0.05. Black\n dashed line (panels E,L) represents the midbrain-hindbrain boundary.</p>", "links"=>[], "tags"=>["ontogeny", "midbrain", "da"], "article_id"=>457001, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018373.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Wnt5a_expression_in_the_ontogeny_of_the_midbrain_DA_axon_/457001", "title"=>"Wnt5a expression in the ontogeny of the midbrain DA axon.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-03-31 01:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/787148"], "description"=>"<p>(<b>A</b>) Whilst sFRP-1 and Wnt5a blocking antibody (αWnt5a)\n were capable of reducing neurite length in E13.5 VM rat primary cultures\n under control conditions (presumably due to antagonism of endogenous Wnt\n signaling), in the presence of Wnt5a they significantly reduced neurite\n length compared to Wnt5a alone. (<b>B</b>–<b>G</b>)\n Examples of Wnt antagonism in VM cultures ± Wnt5a treatment.\n Q-PCR analysis revealed that the Wnt-related receptors Fz3\n (<b>H</b>') and Ryk (<b>I</b>') were highly\n expressed in the VM compared to the dorsal midbrain (DM) and whole\n embryo (E). Furthermore, Fz3 (<b>H”</b>) and Ryk\n (<b>I”</b>) showed significantly higher expression\n within DA neurons (GFP<sup>+</sup>) compared to other cells\n (GFP<sup>−</sup>) isolated from the VM of TH-GFP mice.\n (<b>J</b>) Wnt5a (300 ng/ml) activated Dvl2 in SN4741 cells,\n an effect that could be blocked by αFz3-CRD (3 µg/ml) or\n RYK-Fc (3 µg/ml). (<b>K</b>) E13.5 rat primary VM cultures\n showed that the effects of Wnt5a on DA neurite length were specific,\n illustrated by antagonism with RYK-Fc, and mediated through the Fz3\n receptors, illustrated by blocking of Fz3 with αFz3-CRD.\n (<b>L-Q</b>) Photomicrographs illustrating the effects of\n Wnt5a ± αFz3-CRD or RYK-Fc on DA neurite length. Cells were\n cultured for 3DIV. Scale bar  = 100 µm. Data\n represents mean ± s.e.m., n = 4–5\n cultures. Significantly different from control: #p<0.05, ###\n p<0.001. Significantly different from Wnt5a: * p<0.05,\n ** p<0.005.</p>", "links"=>[], "tags"=>["wnt5a", "da", "neuritogenesis", "and", "mediated"], "article_id"=>457511, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018373.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effects_of_Wnt5a_protein_on_DA_neuritogenesis_are_specific_and____mediated_by_Frizzled_/457511", "title"=>"The effects of Wnt5a protein on DA neuritogenesis are specific and\n mediated by Frizzled.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-03-31 02:05:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/786820"], "description"=>"<p>(<b>A</b>) Wnt5a recombinant protein promoted TH<sup>+</sup>\n neurite elongation in a dose-responsive manner in mouse E11.5 VM primary\n cultures. (<b>A</b>') Wnt5a activated Dvl2 in a\n dose-responsive manner in the SN4741 dopaminergic cell line. Note the\n mobility shift of the Dvl2 protein with increasing doses of Wnt5a.\n (<b>B</b>) Photomicrographs illustrating the complexity of DA\n neurons under control conditions, and (<b>C</b>) following Wnt5a\n treatment. (<b>D</b>) Wnt5a induced a three-fold increase in total\n neurite length compared to control. (<b>E</b>) The effect of Wnt5a\n was specific to the dominant neurite (presumably the DA axon). Wnt5a\n protein reduced the number of (<b>F</b>) DA neurites and\n (<b>G</b>) DA neuritic branches per neuron. (<b>H</b>)\n Immunocytochemistry for TUJ1 revealed that the effects of Wnt5a within\n the VM were specific to DA neurons, with no change in neurite length\n observed for other neurons in culture. (<b>I</b>) Compared to\n control cultures, (<b>J</b>) Wnt5a had no effect on neurite length\n of TUJ-labeled cells. Cells were analyzed after 3DIV. Scale\n bar = 25 µm. Data represents mean ±\n s.e.m., n = 4–5 cultures; * p<0.05,\n ** p<0.01, *** p<0.001.</p>", "links"=>[], "tags"=>["da", "axon", "elongation", "alters", "neuron", "during", "initiation", "neurite"], "article_id"=>457180, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018373.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Wnt5a_promotes_DA_axon_elongation_and_alters_neuron_complexity_during____the_period_of_initiation_of_neurite_outgrowth_/457180", "title"=>"Wnt5a promotes DA axon elongation and alters neuron complexity during\n the period of initiation of neurite outgrowth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-03-31 01:59:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/787979"], "description"=>"<p>(<b>A</b>) In wildtype mice, at E11.5-12, a high ventricular to low\n mantle zone expression of Wnt5a (red shading) in the ventral midbrain,\n combined with our in vitro findings of Wnt5a's ability to elongate and\n repel DA axons (green), suggests that Wnt5a may be capable of polarizing and\n driving DA axons out of the VM. Higher Wnt5a levels in the rostral VM (red),\n in combination with its chemorepulsive function, further suggests that Wnt5a\n may prevent premature rostral trajectory of these DA axons. (<b>B</b>)\n At E14.5, a higher caudal to lower rostral Wnt5a gradient (red), combined\n with the maintained repulsive action of Wnt5a at this age, may ensure\n TH<sup>+</sup> axons maintain their forebrain trajectory. The\n ability of Wnt5a to induce axon retraction in vitro (as shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018373#pone-0018373-g003\" target=\"_blank\">Fig. 3</a>) suggests a\n plausible role in axon stalling, a key developmental event that prevents\n axons prematurely entering their forebrain striatal targets. The dotted red\n line indicates the border of the ganglionic eminence where axon stalling\n occurs. (<b>C</b>) At E18, low expression of Wnt5a is maintained\n within the VM. At this stage in development TH<sup>+</sup> axons are\n present within the GE and are making increasing synaptic contacts.\n (<b>D</b>) In the absence of Wnt5a, at E11.5-12,\n TH<sup>+</sup> axons maintain a rostral projection but are shorter\n and show a lack of organization. (<b>E</b>) By E18, the\n disorganization of TH<sup>+</sup> fibers is evident by the\n defasiculation of the MFB in Wnt5a<sup>−/−</sup> mice.\n Additionally, axons prematurely enter the target, presumably due to loss of\n axonal stalling, resulting in increased striatal innervation in\n Wnt5a<sup>−/−</sup> mice. Lv, lateral ventricle; Aq,\n aquaduct; GE, ganglionic eminence; MFB, medial forebrain bundle.</p>", "links"=>[], "tags"=>["da", "pathways"], "article_id"=>458346, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018373.g008", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_of_Wnt5a_s_role_in_the_development_of_the_DA____mesostriatal_mesolimbic_pathways_in_mice_/458346", "title"=>"Model of Wnt5a's role in the development of the DA\n mesostriatal/mesolimbic pathways in mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-03-31 02:19:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/786977"], "description"=>"<p>(<b>A</b>) At a time when DA axons would normally be approaching\n their striatal targets (mouse E14.5), treatment with Wnt5a protein\n caused retraction of TH<sup>+</sup> neurites, and more specifically\n (<b>B</b>) DA axons (dominant neurite length). Wnt5a had no\n effect on the complexity of DA neurons, as assessed by (<b>C</b>)\n neurite number and (<b>D</b>) neurite branching. Photomicrographs\n illustrating examples of neurite retraction following Wnt5a application\n (<b>F</b>), compared to control (<b>E</b>). Cells were\n analyzed after 3DIV. Scale bar = 25 µm. Data\n represents mean ± s.e.m., n = 4–5\n cultures, *** p<0.001.</p>", "links"=>[], "tags"=>["causes", "da", "neurite", "retraction", "older", "ventral", "midbrain"], "article_id"=>457336, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018373.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Wnt5a_causes_DA_neurite_retraction_in_older_ventral_midbrain____cultures_/457336", "title"=>"Wnt5a causes DA neurite retraction in older ventral midbrain\n cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-03-31 02:02:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/787775"], "description"=>"<p>(<b>A</b>) Sagittal image of the\n <i>Wnt5a</i><sup>+/+</sup> and (<b>B</b>)\n <i>Wnt5a</i><sup>−/−</sup> brain demonstrating\n morphological changes within the dopaminergic pathway. Note the\n broadening of the MFB in\n <i>Wnt5a</i><sup>−/−</sup> compared to\n <i>Wnt5a</i><sup>+/+</sup> mice, indicated by\n arrows, as well as increased terminal innervation in the dorsal striatum\n (<b>A</b>' and <b>B</b>'). (<b>C</b>)\n <i>Wnt5a</i><sup>−/−</sup> mice showed\n defasciculation of the MFB as revealed by the increased volume occupied\n by TH<sup>+</sup> fibers. (<b>D</b>) Within the MFB,\n <i>Wnt5a</i><sup>−/−</sup> mice had\n significantly more TH<sup>+</sup> fibers at proximal (320 µm)\n levels of the MFB. (<b>E</b>)\n <i>Wnt5a</i><sup>−/−</sup> mice also had\n significantly more TH<sup>+</sup> terminals within the lateral\n striatum than <i>Wnt5a<sup>+/+</sup></i> mice.\n (<b>F</b>) Image illustrating the level of the MFB at which\n neurite counts were performed (HP, hippocampus; Ctx, cortex).\n (<b>I</b>) Image illustrating the area of the lateral striatum\n delineated for stereological estimates of TH<sup>+</sup> terminal\n density. (<b>G</b>–<b>K</b>) Confocal photomicrographs\n illustrating differences in the midbrain dopaminergic pathway of\n <i>Wnt5a</i><sup>+/+</sup> and\n <i>Wnt5a</i><sup>−/−</sup> mice, respectively,\n including (<b>G,J</b>) broadening of the MFB,\n (<b>G</b>'<b>,J</b>') increased neurites\n within the MFB (320 µm from the DA neurons in the VM) and\n (<b>H,K</b>) increased terminal density in the lateral\n striatum. Insert in (<b>H</b>) illustrates individual\n TH<sup>+</sup> terminals). Data represents mean ±\n s.e.m., n = 4–7 embryos/geneotype; *\n p<0.05, ** p<0.01, *** p<0.001.</p>", "links"=>[], "tags"=>["mice", "abnormal", "fasciculation", "da", "axons", "median", "forebrain", "bundle", "changes", "terminal"], "article_id"=>458131, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018373.g007", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Wnt5a_8722_8722_mice____display_abnormal_fasciculation_of_the_DA_axons_in_the_median_forebrain____bundle_MFB_and_changes_in_DA_fiber_and_terminal_density_/458131", "title"=>"<i>Wnt5a</i><sup><b>−/−</b></sup> mice\n display abnormal fasciculation of the DA axons in the median forebrain\n bundle (MFB) and changes in DA fiber and terminal density.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-03-31 02:15:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/787340"], "description"=>"<p>Select antagonists were used to identify the downstream signaling pathway\n responsible for mediating the effects of Wnt5a on DA neurites.\n Antagonism of the canonical Wnt pathway (using Dkk1 recombinant\n protein), the canonical and non-canonical Wnt pathways (using casein\n kinase 1 inhibitor, D4476) and even more selectively the non-canonical\n PCP pathway (using Rac1 inhibitor, NSC23766) revealed that the effect of\n Wnt5a on (<b>A</b>) neurite length and (<b>B</b>) neurite\n number were mediated by the non-canonical PCP pathway (D4476 and\n NSC23766 both significantly antagonizing the effects of Wnt5a).\n (<b>C</b>–<b>F</b>) Examples of changes in DA\n neuron morphology following treatment with Wnt5a ± selective\n antagonists. Scale bar  = 50 µm. Data\n represents mean ± s.e.m., n = 4–5\n cultures; ** p<0.01, *** p<0.001.</p>", "links"=>[], "tags"=>["wnt5a", "elongation", "mediated", "rac1", "the", "non-canonical"], "article_id"=>457700, "categories"=>["Molecular Biology", "Neuroscience", "Developmental Biology"], "users"=>["Brette D. Blakely", "Christopher R. Bye", "Chathurini V. Fernando", "Malcolm K. Horne", "Maria L. Macheda", "Steven A. Stacker", "Ernest Arenas", "Clare L. Parish"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018373.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effects_of_Wnt5a_on_elongation_are_mediated_through_Rac1_of_the____non_canonical_Wnt_PCP_pathway_/457700", "title"=>"The effects of Wnt5a on elongation are mediated through Rac1 of the\n non-canonical Wnt/PCP pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-03-31 02:08:20"}

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Relative Metric

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