Tau's role in the developing brain: implications for intellectual disability
Microdeletions encompassing the MAPT (Tau) locus resulting in intellectual disability raised the hypothesis that Tau may regulate early functions in the developing brain. Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge...
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| Veröffentlicht in: | Human molecular genetics 2012-04, Vol.21 (8), p.1681-1692 |
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| container_title | Human molecular genetics |
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| creator | SAPIR, Tamar FROTSCHER, Michael LEVY, Talia MANDELKOW, Eva-Maria REINED, Orly |
| description | Microdeletions encompassing the MAPT (Tau) locus resulting in intellectual disability raised the hypothesis that Tau may regulate early functions in the developing brain. Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge of radially migrating neurons was aberrant in spite of normal morphology of radial glia. Furthermore, intracellular mitochondrial transport and morphology were affected. In early postnatal brains, a portion of Tau knocked down neurons reached the cortical plate. Nevertheless, they exhibited far less developed dendrites and a striking reduction in connectivity evident by the size of boutons. Our novel results strongly implicate MAPT as a dosage-sensitive gene in this locus involved in intellectual disability. Furthermore, our results are likely to impact our understanding of other diseases involving Tau. |
| doi_str_mv | 10.1093/hmg/ddr603 |
| format | Article |
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Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge of radially migrating neurons was aberrant in spite of normal morphology of radial glia. Furthermore, intracellular mitochondrial transport and morphology were affected. In early postnatal brains, a portion of Tau knocked down neurons reached the cortical plate. Nevertheless, they exhibited far less developed dendrites and a striking reduction in connectivity evident by the size of boutons. Our novel results strongly implicate MAPT as a dosage-sensitive gene in this locus involved in intellectual disability. Furthermore, our results are likely to impact our understanding of other diseases involving Tau.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddr603</identifier><identifier>PMID: 22194194</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult and adolescent clinical studies ; Animals ; Axons - ultrastructure ; Biological and medical sciences ; Brain ; Brain - cytology ; Brain - embryology ; Brain - metabolism ; Cell migration ; Cell Movement ; Cell Shape ; Cells, Cultured ; Cortex ; Dendrites ; Dendrites - ultrastructure ; Electroporation ; Embryo, Mammalian ; Embryonic Development ; Fundamental and applied biological sciences. Psychology ; Gene Knockdown Techniques ; Genetics of eukaryotes. Biological and molecular evolution ; Intellectual deficiency ; Intellectual Disability - genetics ; Intellectual Disability - metabolism ; Medical sciences ; Mental retardation ; Mice ; Mitochondria ; Mitochondria - ultrastructure ; Molecular and cellular biology ; Neural networks ; Neuroglia - ultrastructure ; Neurons ; Neurons - cytology ; Neurons - physiology ; Neurons - ultrastructure ; Presynapse ; Presynaptic Terminals - ultrastructure ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; radial glial cells ; RNA, Small Interfering ; Tau protein ; tau Proteins - genetics ; tau Proteins - metabolism</subject><ispartof>Human molecular genetics, 2012-04, Vol.21 (8), p.1681-1692</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-23abd2545a0c45a71cb1038d58de0594175e9a84b8049935e602b801747667653</citedby><cites>FETCH-LOGICAL-c451t-23abd2545a0c45a71cb1038d58de0594175e9a84b8049935e602b801747667653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25767692$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22194194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SAPIR, Tamar</creatorcontrib><creatorcontrib>FROTSCHER, Michael</creatorcontrib><creatorcontrib>LEVY, Talia</creatorcontrib><creatorcontrib>MANDELKOW, Eva-Maria</creatorcontrib><creatorcontrib>REINED, Orly</creatorcontrib><title>Tau's role in the developing brain: implications for intellectual disability</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>Microdeletions encompassing the MAPT (Tau) locus resulting in intellectual disability raised the hypothesis that Tau may regulate early functions in the developing brain. Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge of radially migrating neurons was aberrant in spite of normal morphology of radial glia. Furthermore, intracellular mitochondrial transport and morphology were affected. In early postnatal brains, a portion of Tau knocked down neurons reached the cortical plate. Nevertheless, they exhibited far less developed dendrites and a striking reduction in connectivity evident by the size of boutons. Our novel results strongly implicate MAPT as a dosage-sensitive gene in this locus involved in intellectual disability. Furthermore, our results are likely to impact our understanding of other diseases involving Tau.</description><subject>Adult and adolescent clinical studies</subject><subject>Animals</subject><subject>Axons - ultrastructure</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>Brain - cytology</subject><subject>Brain - embryology</subject><subject>Brain - metabolism</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell Shape</subject><subject>Cells, Cultured</subject><subject>Cortex</subject><subject>Dendrites</subject><subject>Dendrites - ultrastructure</subject><subject>Electroporation</subject><subject>Embryo, Mammalian</subject><subject>Embryonic Development</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Knockdown Techniques</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Intellectual deficiency</subject><subject>Intellectual Disability - genetics</subject><subject>Intellectual Disability - metabolism</subject><subject>Medical sciences</subject><subject>Mental retardation</subject><subject>Mice</subject><subject>Mitochondria</subject><subject>Mitochondria - ultrastructure</subject><subject>Molecular and cellular biology</subject><subject>Neural networks</subject><subject>Neuroglia - ultrastructure</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Neurons - physiology</subject><subject>Neurons - ultrastructure</subject><subject>Presynapse</subject><subject>Presynaptic Terminals - ultrastructure</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>radial glial cells</subject><subject>RNA, Small Interfering</subject><subject>Tau protein</subject><subject>tau Proteins - genetics</subject><subject>tau Proteins - metabolism</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EtLAzEQB_AgitbqxQ8guUhFWJtsXhtvUnxBwUs9L9kk20ayD5Ndod_eSKvehIEM4ccw8wfgAqNbjCSZb5r13JjAETkAE0w5ynJUkEMwQZLTjEvET8BpjO8IYU6JOAYneY4lTTUBy5UaZxGGzlvoWjhsLDT20_qud-0aVkG59g66pvdOq8F1bYR1F5IcrPdWD6Py0LioKufdsD0DR7Xy0Z7v3yl4e3xYLZ6z5evTy-J-mWnK8JDlRFUmZ5QplD6UwLrCiBSGFcYilhYTzEpV0KpAVErCLEd56rGggnPBGZmC2W5uH7qP0cahbFzUaSPV2m6MpWQSU0qwSPL6X4kRKgoiGeOJ3uyoDl2MwdZlH1yjwjah8jvnMuVc7nJO-HI_d6waa37pT7AJXO2Bilr5OqhWu_jnmEiXyJx8AYauhJI</recordid><startdate>20120415</startdate><enddate>20120415</enddate><creator>SAPIR, Tamar</creator><creator>FROTSCHER, Michael</creator><creator>LEVY, Talia</creator><creator>MANDELKOW, Eva-Maria</creator><creator>REINED, Orly</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20120415</creationdate><title>Tau's role in the developing brain: implications for intellectual disability</title><author>SAPIR, Tamar ; FROTSCHER, Michael ; LEVY, Talia ; MANDELKOW, Eva-Maria ; REINED, Orly</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-23abd2545a0c45a71cb1038d58de0594175e9a84b8049935e602b801747667653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Animals</topic><topic>Axons - ultrastructure</topic><topic>Biological and medical sciences</topic><topic>Brain</topic><topic>Brain - cytology</topic><topic>Brain - embryology</topic><topic>Brain - metabolism</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell Shape</topic><topic>Cells, Cultured</topic><topic>Cortex</topic><topic>Dendrites</topic><topic>Dendrites - ultrastructure</topic><topic>Electroporation</topic><topic>Embryo, Mammalian</topic><topic>Embryonic Development</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Knockdown Techniques</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Intellectual deficiency</topic><topic>Intellectual Disability - genetics</topic><topic>Intellectual Disability - metabolism</topic><topic>Medical sciences</topic><topic>Mental retardation</topic><topic>Mice</topic><topic>Mitochondria</topic><topic>Mitochondria - ultrastructure</topic><topic>Molecular and cellular biology</topic><topic>Neural networks</topic><topic>Neuroglia - ultrastructure</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Neurons - physiology</topic><topic>Neurons - ultrastructure</topic><topic>Presynapse</topic><topic>Presynaptic Terminals - ultrastructure</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>radial glial cells</topic><topic>RNA, Small Interfering</topic><topic>Tau protein</topic><topic>tau Proteins - genetics</topic><topic>tau Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SAPIR, Tamar</creatorcontrib><creatorcontrib>FROTSCHER, Michael</creatorcontrib><creatorcontrib>LEVY, Talia</creatorcontrib><creatorcontrib>MANDELKOW, Eva-Maria</creatorcontrib><creatorcontrib>REINED, Orly</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SAPIR, Tamar</au><au>FROTSCHER, Michael</au><au>LEVY, Talia</au><au>MANDELKOW, Eva-Maria</au><au>REINED, Orly</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tau's role in the developing brain: implications for intellectual disability</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2012-04-15</date><risdate>2012</risdate><volume>21</volume><issue>8</issue><spage>1681</spage><epage>1692</epage><pages>1681-1692</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><abstract>Microdeletions encompassing the MAPT (Tau) locus resulting in intellectual disability raised the hypothesis that Tau may regulate early functions in the developing brain. Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge of radially migrating neurons was aberrant in spite of normal morphology of radial glia. Furthermore, intracellular mitochondrial transport and morphology were affected. In early postnatal brains, a portion of Tau knocked down neurons reached the cortical plate. Nevertheless, they exhibited far less developed dendrites and a striking reduction in connectivity evident by the size of boutons. Our novel results strongly implicate MAPT as a dosage-sensitive gene in this locus involved in intellectual disability. Furthermore, our results are likely to impact our understanding of other diseases involving Tau.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>22194194</pmid><doi>10.1093/hmg/ddr603</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult and adolescent clinical studies Animals Axons - ultrastructure Biological and medical sciences Brain Brain - cytology Brain - embryology Brain - metabolism Cell migration Cell Movement Cell Shape Cells, Cultured Cortex Dendrites Dendrites - ultrastructure Electroporation Embryo, Mammalian Embryonic Development Fundamental and applied biological sciences. Psychology Gene Knockdown Techniques Genetics of eukaryotes. Biological and molecular evolution Intellectual deficiency Intellectual Disability - genetics Intellectual Disability - metabolism Medical sciences Mental retardation Mice Mitochondria Mitochondria - ultrastructure Molecular and cellular biology Neural networks Neuroglia - ultrastructure Neurons Neurons - cytology Neurons - physiology Neurons - ultrastructure Presynapse Presynaptic Terminals - ultrastructure Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry radial glial cells RNA, Small Interfering Tau protein tau Proteins - genetics tau Proteins - metabolism |
| title | Tau's role in the developing brain: implications for intellectual disability |
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