Regulation of Emx2 Expression by Antisense Transcripts in Murine Cortico-Cerebral Precursors
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{"title"=>"Regulation of Emx2 expression by antisense transcripts in murine cortico-cerebral precursors", "type"=>"journal", "authors"=>[{"first_name"=>"Giulia", "last_name"=>"Spigoni", "scopus_author_id"=>"35754731700"}, {"first_name"=>"Chiara", "last_name"=>"Gedressi", "scopus_author_id"=>"6505476291"}, {"first_name"=>"Antonello", "last_name"=>"Mallamaci", "scopus_author_id"=>"6701662843"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"77952514762", "doi"=>"10.1371/journal.pone.0008658", "issn"=>"19326203", "pui"=>"358394602", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"20066053", "scopus"=>"2-s2.0-77952514762"}, "id"=>"872927da-79be-339d-b6ed-81ff3d9aebb1", "abstract"=>"BACKGROUND:Emx2 encodes for a transcription factor expressed in the embryonic intermediate mesoderm and central nervous system (CNS). It is implicated in several aspects of cerebral cortex development, including morphogenetic field specification, arealization, precursor proliferation and lamination. Four Emx2-associated antisense transcripts have been found in the urogenital system; one of them, Emx2OS, has been also detected in the adult brain. Until now, however, nothing is known about expression and function of Emx2OS in the developing CNS.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS:By quantitative RT-PCR and in situ hybridization, we reconstructed the Emx2OS expression profile in the embryonic CNS, paying special attention to the developing cerebral cortex. Emx2OS was observed in a number of CNS structures expressing also Emx2. Within the cortex, Emx2OS was detectable in periventricular precursors, expressing the sense transcript, and peaked in newly born post-mitotic neurons not expressing such transcript. By integrating lentiviral gene delivery, RNAi, TetON technology, morpholino-mediated gene knock-down, drug-induced perturbation of gene expression, and quantitative RT-PCR, we addressed possible roles of Ex2 antisense RNA in Emx2 regulation, in primary CNS precursor cultures. We found that, in both cortical precursors and their neuronal progenies, Emx2 antisense RNA contributes to post-transcriptional down-regulation of its sense partner, possibly by a Dicer-promoted mechanism. The same RNA, when delivered to rhombo-spinal precursors, stimulates ectopic expression of Emx2, whereas Emx2 knock-out dramatically impairs Emx2OS transcription. This suggests that, within the developing CNS, a reciprocal Emx2/Emx2OS regulatory loop may normally sustain transcription at the Emx2 locus.\\n\\nCONCLUSIONS/SIGNIFICANCE:This study shows that antisense transcripts may contribute to developmental regulation of a key transcription factor gene implicated in CNS patterning, possibly by complex and multilevel mechanisms. The activation of Emx2 by a short antisense transcript may be a prototype of a method for overexpressing single specific genes, without introducing additional copies of them into the genome.", "link"=>"http://www.mendeley.com/research/regulation-emx2-expression-antisense-transcripts-murine-corticocerebral-precursors", "reader_count"=>31, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Researcher"=>10, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Researcher"=>10, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>22, "Medicine and Dentistry"=>1, "Neuroscience"=>3, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>22}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}}, "reader_count_by_country"=>{"United Kingdom"=>3}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/431195"], "description"=>"<div><h3>Background</h3><p><em>Emx2</em> encodes for a transcription factor expressed in the embryonic intermediate mesoderm and central nervous system (CNS). It is implicated in several aspects of cerebral cortex development, including morphogenetic field specification, arealization, precursor proliferation and lamination. Four <em>Emx2</em>-associated antisense transcripts have been found in the urogenital system; one of them, <em>Emx2OS</em>, has been also detected in the adult brain. Until now, however, nothing is known about expression and function of <em>Emx2OS</em> in the developing CNS.</p><h3>Methodology/Principal Findings</h3><p>By quantitative RT-PCR and in situ hybridization, we reconstructed the <em>Emx2OS</em> expression profile in the embryonic CNS, paying special attention to the developing cerebral cortex. <em>Emx2OS</em> was observed in a number of CNS structures expressing also <em>Emx2</em>. Within the cortex, <em>Emx2OS</em> was detectable in periventricular precursors, expressing the sense transcript, and peaked in newly born post-mitotic neurons not expressing such transcript. By integrating lentiviral gene delivery, RNAi, TetON technology, morpholino-mediated gene knock-down, drug-induced perturbation of gene expression, and quantitative RT-PCR, we addressed possible roles of <em>Ex2</em> antisense RNA in <em>Emx2</em> regulation, in primary CNS precursor cultures. We found that, in both cortical precursors and their neuronal progenies, <em>Emx2</em> antisense RNA contributes to post-transcriptional down-regulation of its sense partner, possibly by a Dicer-promoted mechanism. The same RNA, when delivered to rhombo-spinal precursors, stimulates ectopic expression of <em>Emx2</em>, whereas <em>Emx2</em> knock-out dramatically impairs <em>Emx2OS</em> transcription. This suggests that, within the developing CNS, a reciprocal <em>Emx2</em>/<em>Emx2OS</em> regulatory loop may normally sustain transcription at the <em>Emx2</em> locus.</p><h3>Conclusions/Significance</h3><p>This study shows that antisense transcripts may contribute to developmental regulation of a key transcription factor gene implicated in CNS patterning, possibly by complex and multilevel mechanisms. The activation of <em>Emx2</em> by a short antisense transcript may be a prototype of a method for overexpressing <em>single specific</em> genes, without introducing additional copies of them into the genome.</p></div>", "links"=>[], "tags"=>["antisense", "transcripts", "murine", "cortico-cerebral", "precursors"], "article_id"=>145097, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Regulation_of_Emx2_Expression_by_Antisense_Transcripts_in_Murine_Cortico_Cerebral_Precursors/145097", "title"=>"Regulation of <em>Emx2</em> Expression by Antisense Transcripts in Murine Cortico-Cerebral Precursors", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 01:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/868517"], "description"=>"<p>(A) Representation of the murine <i>Emx2</i> locus, with the <i>Emx2</i>-mRNA and the <i>Emx2OS</i>-ncRNA transcription units (red). Genomic localization of the riboprobe used for <i>in situ</i> hybridization analysis of <i>Emx2OS</i> (blue bar). Genomic localization of the oligonucleotides employed for quantitative RT-PCR evaluation of <i>Emx2OS</i>-ncRNA (P1 and P3), <i>Emx2</i>-mRNA (N2F and N2R) and <i>Emx2</i>-pre-mRNA (I1, I2, I3 and I4) (blue arrowheads). (B) Structure of the bi-cistronic plasmids employed for assaying activities of artificial miRNAs against <i>Emx2OS</i>-ncRNA in HeLa cells and of lentivectors for overexpressing these miRNAs in primary cells. Localization of miR-α<i>Emx2</i>OS-542 and -774 (blue arrowheads) as well as of their responsive element, <i>miR-RE</i>, with respect to the antisense transcript. <i>miR-RE</i> (dark yellow), showed enlarged over the antisense transcript, extends across the 3<sup>rd</sup> and the 4<sup>th</sup> exons of it. (C) Structure of the “driver” lentivector, guiding constitutive expression of rtTA2<sup>S</sup>-M2, and of “expressor” lentivectors, guiding rtTA/doxycycline-dependent expression of ncRNA/IRES/eGFPcds modules. Genomic localization of OS1-179(+) and OS1-179(−) ncRNAs (blue arrows), as compared to <i>Emx2OS</i>-ncRNA and <i>Emx2</i>-mRNA (for sake of clarity, the sense/antisense ovarlapping region and its surroundings are represented enlarged; red, non coding sequences; violet, coding sequences).</p>", "links"=>[], "tags"=>["molecular", "tools", "studying"], "article_id"=>538978, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Synopsis_of_molecular_tools_used_for_studying_expression_and_function_of_Emx2OS_/538978", "title"=>"Synopsis of molecular tools used for studying expression and function of <i>Emx2OS</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 02:29:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/868640"], "description"=>"<p>Sense and antisense transcripts display concordant spatial distributions (abundant in the cortex, absent in rhombencephalon), from E10.5 to E18.5. Within the cortex, they share a similar temporal trend, being progressively down-regulated from the pre-neuronogenic (E10.5) to post-neuronogenic stages (E18.5). RTs are primed by random hexamers and PCRs by oligos shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008658#pone-0008658-g001\" target=\"_blank\">Fig. 1</a>. Data are normalized on E10.5 cortical samples. Abbreviations: c, cortex; r, rhombencephalon.</p>", "links"=>[], "tags"=>["quantitative", "rt-pcr", "cortex"], "article_id"=>539098, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Time_course_quantitative_RT_PCR_analysis_of_Emx2_mRNA_and_Emx2OS_ncRNA_expression_in_the_developing_cortex_and_rhombencephalon_/539098", "title"=>"Time-course quantitative RT-PCR analysis of <i>Emx2</i>-mRNA and <i>Emx2OS</i>-ncRNA expression in the developing cortex and rhombencephalon.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 02:31:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/868797"], "description"=>"<p>(A–D) Within the E12.5 developing CNS, <i>Emx2OS</i>-ncRNA is detectable in telencephalon (A,B), mesencephalon (me), including both tectum (te) and tegmentum (tg), (panels A,C) and diencephalon, including the mammillary recess (arrowhead in panel A). It is not present in rhombencephalon (rh, panel G), except the choroid plexus of the IV ventricle (chp, panels A,D). Outside the CNS, <i>Emx2OS</i> is expressed in primordia of sense organs, nasal pits (np, panel E) and otic vesicle (ov, panel G), as well as in mesenchyme underlying snout epidermis (A, asterisk) and surrounding the hypothalamic (hy) optic recess (F, arrowheads). Scalebars, 200 µm in A–C, 50 µm in D–G.</p>", "links"=>[], "tags"=>["transcripts", "embryonic"], "article_id"=>539258, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_Emx2OS_transcripts_in_the_embryonic_E12_5_mouse_brain_/539258", "title"=>"Distribution of <i>Emx2OS</i> transcripts in the embryonic E12.5 mouse brain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 02:34:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/868986"], "description"=>"<p>Distribution of <i>Emx2OS</i>-ncRNA (A–I) and <i>Reln</i>-mRNA (J–L) on mid-frontal sections of E12.5 (A), E14.5 (B) and E18.5 (C,G,J) mouse telencephalons. (D), (E) and (F) are magnifications of boxed areas in (A), (B) and (C), respectively. (H) and (I) are enlargements of boxed areas of panel (G), respectively; the same applies to panels (K) and (L) with respect to (J); (G) and (J) are adjacent sections from the same brain. <i>Emx2OS</i> is expressed in periventricular proliferative layers at all ages subject of analysis (A–C). An additional signal is detectable within the cortical plate starting from E14.5 (B) and gets confined to its marginal-most part at E18.5 (C). No <i>Emx2OS</i> expression can be detected in the neocortical marginal zone (G,H, empty arrowheads) as well as in the archicortical stratum lacunosum-moleculare (G,I), both rich of <i>Reln</i><sup>+</sup> Cajal-Retzius cells (J–L, solid arrowheads). Some aspecific staining may be found in meninges, at the edge of sections. Abbreviations: CA1, cornu Ammonis field 1; CA3, cornu Ammonis field 3; cp, CP, cortical plate; DG, dentate gyrus; HF, hippocampal fissure; iz, intermediate zone; mz, MZ, marginal zone; ppl, preplate; SLM, stratum lacunosum-moleculare; sp, subplate; svz, subventricular zone; vz, ventricular zone; Scalebars, 200 µm.</p>", "links"=>[], "tags"=>["hybridization", "emx2os-ncrna"], "article_id"=>539446, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_situ_hybridization_profile_of_Emx2OS_ncRNA_in_the_developing_mouse_telencephalon_/539446", "title"=>"<i>In situ</i> hybridization profile of Emx2OS-ncRNA in the developing mouse telencephalon.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 02:37:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/869182"], "description"=>"<p>(A) Down-regulation of the miR-RE-sensitized <i>DsRed2</i> reporter in Hela cells, upon overexpression of artificial miRNAs designed against <i>Emx2OS</i>. (B) Down-regulation of <i>Emx2OS</i>-ncRNA, up-regulation of mature <i>Emx2</i>-mRNA and unchanged levels of immature <i>Emx2</i>-pre-mRNA in E12.5-derived cortical primary cells (cx), acutely infected by miR-αEmx2OS-774-expressor lentivirus, kept in Sato medium and harvested 72 hours later. Data are normalized on control-miR-treated samples (miR-C). (C) Neuronal differentiation of lentivirus-transduced neural precursors kept 72 hours under 5% serum, as assessed by β-tubulin immunoprofiling. Down-regulation of <i>Emx2</i>-mRNA in miR-C-infected neural precursors, kept 72 hours under 5% serum in place of growth factors (GFs). Rescue of such down-regulation, elicited via miR-αEmx2OS-774-induced knock-down of <i>Emx2OS</i>-ncRNA. qRT-PCR data are normalized on control-miR-treated samples (miR-C), kept under GFs.</p>", "links"=>[], "tags"=>["knock-down", "hela", "cells", "dissociated", "cortico-cerebral"], "article_id"=>539643, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Emx2OS_knock_down_in_HeLa_cells_and_dissociated_cortico_cerebral_precursors_/539643", "title"=>"<i>Emx2OS</i> knock-down in HeLa cells and dissociated cortico-cerebral precursors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 02:40:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/869306"], "description"=>"<p>(A) <i>Emx2</i>-mRNA and <i>Emx2OS</i>-ncRNA expression in primary neural precursor cells, derived from E12.5 cortices (cx) and acutely infected with the “driver” lentivector, plus “expressor” lentivectors [OS1-179(+), OS1-179(–) and control (C)] in different combinations. One day after sample dissociation, cells are administered with doxycycline and, two more days later, profiled for RNA. Data are normalized on control lentivirus-treated samples. OS1-179(+) induces a moderate, but statistically significant down-regulation of <i>Emx2</i>-mRNA, as well as a moderate up-regulation of the endogenous antisense transcript. (B) <i>Emx2</i>-mRNA expression in NIH/3T3 cells, acutely infected with the “driver” lentivector plus each of the three “expressor” lentivectors [OS1-179(+), OS1-179(-) or C]. Cells are administered 6 hours after infection with an anti-Dicer1 or a control (C) morpholino and 18 more hours later with doxycycline. Two more days later, they are RNA-profiled by qRT-PCR. Data reported in the histogram are normalized on samples infected by control lentivirus and exposed to control morpholino. Compared with lentivirus-C-treated controls, levels of <i>Emx2-mRNA</i> change upon OS1-179(+) infection by a factor of 0.56/1 = 0.56 (p<0.001) and 1.42/1.65 = 0.87 (p<0.01), in NIH/3T3 cells treated by control morpholino and α-Dicer1, respectively. Compared with morpholino-C-treated controls, levels of <i>Emx2</i>-mRNA change upon α-Dicer1 administration by a factor of 1.42/0.56 = 2.54 (p<0.001), 1.65/1 = 1.65 (p<0.001), and 1.82/1.31 = 1.39 (p<0.01), in cells infected by OS1-179(+), control or OS1-179(–) lentiviruses, respectively. Two-ways ANOVA data analysis suggests the occurrence of a functional interaction between Dicer1 and OS1-179(+), with p<0.025 (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008658#pone-0008658-g006\" target=\"_blank\">Fig. 6B</a>).</p>", "links"=>[], "tags"=>["dissociated", "cortico-cerebral", "precursors", "cells"], "article_id"=>539765, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Emx2_and_Emx2OS_expression_in_dissociated_cortico_cerebral_precursors_and_NIH_3T3_cells_upon_OS1_179_delivery_/539765", "title"=>"<i>Emx2</i> and <i>Emx2OS</i> expression in dissociated cortico-cerebral precursors and NIH/3T3 cells upon OS1-179(+) delivery.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 02:42:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/869507"], "description"=>"<p>(A) Ectopic activation of the endogenous <i>Emx2</i> locus by OS1-179(+). The two graphs show <i>Emx2</i>-mRNA and <i>Emx2OS</i>-ncRNA expression levels in primary neural precursors from distinctive portions of the E10.5 CNS, rhombo-spinal tract (rh/sc) and telencephalon (te), acutely infected with “driver” and “expressor” lentivectors (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008658#pone-0008658-g001\" target=\"_blank\">Fig. 1C</a>), kept under doxycycline and added or not with the Li<sup>+</sup>/cyclopamine mix. Samples are RNA-profiled 72 hours after infection. Data are normalized on telencephalic precursors exposed to Li<sup>+</sup>/cyclopamine, infected by control lentivirus and kept under doxycycline. Basal <i>Emx2</i> expression by rhombo-spinal cells, very low as compared to telencephalic precursors, rises about 2 (p<0.01), 4 (p<0.001) and 30 times (p<0.001), upon treatment of these cells with the OS1-179(+) virus, the drug mix, or both, respectively. Two-ways ANOVA indicates that a specific interaction between OS1-179(+) and the drug mix takes place, with p<0.001. A similar course is shown by <i>Emx2OS</i>-ncRNA. (B) Reversibility of OS1-179(+)-dependent activation of the endogenous <i>Emx2</i> transcription unit. The four panels to the top show time course analysis of eGFP fluorescence in neural precursors, infected by driver and OS1-179(+) lentiviruses and kept under doxycycline for 72 or 120 hours. The absence of fluorescence in the bottom-right panel means that withdrawal of doxycycline at 72 hours is sufficient to reset levels of the eGFP/OS1-179(+) chimaeric transcript to zero by 120 hours. The two graphs to the bottom show <i>Emx2</i>-mRNA and <i>Emx2OS</i>-ncRNA expression levels in primary neural precursors from the E10.5 rhombo-spinal (rh/sc) tract, acutely infected with “driver” and “expressor” lentivectors (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008658#pone-0008658-g001\" target=\"_blank\">Fig. 1C</a>), kept under doxycycline for 72 or 120 hours and chronically exposed to Li<sup>+</sup>/cyclopamine throughout the experiment. Samples are RNA-profiled 120 hours after infection. Data are normalized on rhombo-spinal cells exposed to Li<sup>+</sup>/cyclopamine, infected by OS1-179(+) lentivirus and kept under doxycycline throughout the experiment. Removal of doxycycline at 72 hours abolishes (p<0.01) the 4-fold up-regulation of <i>Emx2</i>-mRNA, detectable in Li/cyclopamine-treated rhombo-spinal precursors, upon their further infection by lentivirus OS1-179(+) (p<0.01). Similar consequences are elicited by doxycycline removal on levels of <i>Emx2OS</i>-ncRNA.</p>", "links"=>[], "tags"=>["activation", "rhombo-spinal"], "article_id"=>539963, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ectopic_activation_of_Emx2_mRNA_and_Emx2OS_ncRNA_in_rhombo_spinal_neurospheres_upon_OS1_179_delivery_/539963", "title"=>"Ectopic activation of <i>Emx2</i>-mRNA and <i>Emx2OS</i>-ncRNA in rhombo-spinal neurospheres, upon OS1-179(+) delivery.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 02:46:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/869709"], "description"=>"<p>Abbreviations: wt, wild type; he, heterozygous; ko, knock-out.</p>", "links"=>[], "tags"=>["acutely", "dissected", "cortices", "null", "mutant"], "article_id"=>540165, "categories"=>["Developmental Biology", "Neuroscience"], "users"=>["Giulia Spigoni", "Chiara Gedressi", "Antonello Mallamaci"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008658.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Down_regulation_of_Emx2_mRNA_and_Emx2OS_ncRNA_in_acutely_dissected_cortices_from_E12_5_Emx2_null_mutant_embryos_/540165", "title"=>"Down-regulation of <i>Emx2</i>-mRNA and <i>Emx2OS</i>-ncRNA in acutely dissected cortices from E12.5 <i>Emx2</i> null mutant embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-01-11 00:02:45"}

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Relative Metric

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