{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:59Z","timestamp":1785428099802,"version":"3.56.0"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,5,9]],"date-time":"2017-05-09T00:00:00Z","timestamp":1494288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>Mutations in <jats:italic><jats:styled-content style=\"fixed-case\">FAT<\/jats:styled-content>4<\/jats:italic> gene, one of the human <jats:italic><jats:styled-content style=\"fixed-case\">FAT<\/jats:styled-content><\/jats:italic> family genes, have been identified in Van Maldergem syndrome (<jats:styled-content style=\"fixed-case\">VMS<\/jats:styled-content>) and Hennekam lymphangiectasia\u2010lymphedema syndrome (<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>). The <jats:italic><jats:styled-content style=\"fixed-case\">FAT<\/jats:styled-content>4<\/jats:italic> gene encodes a large protein with extracellular cadherin repeats, <jats:styled-content style=\"fixed-case\">EGF<\/jats:styled-content>\u2010like domains and Laminin G\u2010like domains. <jats:styled-content style=\"fixed-case\">FAT<\/jats:styled-content>4 plays a role in tumor suppression and planar cell polarity. <jats:italic>Drosophila<\/jats:italic> contains a human <jats:italic><jats:styled-content style=\"fixed-case\">FAT<\/jats:styled-content>4<\/jats:italic> homologue, <jats:italic>fat. Drosophila fat<\/jats:italic> has been mainly studied with <jats:italic>Drosophila<\/jats:italic> eye and wing systems. Here, we specially knocked down <jats:italic>Drosophila fat<\/jats:italic> in nerve system. Neuron\u2010specific knockdown of <jats:italic>fat<\/jats:italic> shortened the life span and induced the defect in locomotive abilities of adult flies. In consistent with these phenotypes, defects in synapse structure at neuromuscular junction were observed in neuron\u2010specific <jats:italic>fat<\/jats:italic>\u2010knockdown flies. In addition, aberrations in axonal targeting of photoreceptor neuron in third\u2010instar larvae were also observed, suggesting that fat involves in axonal targeting. Taken together, the results indicate that <jats:italic>Drosophila fat<\/jats:italic> plays an essential role in formation and\/or maintenance of neuron. Both <jats:styled-content style=\"fixed-case\">VMS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> show mental retardation and neuronal defects. We therefore consider that these two rare human diseases could possibly be caused by the defect in <jats:italic><jats:styled-content style=\"fixed-case\">FAT<\/jats:styled-content>4<\/jats:italic> function in neuronal cells.<\/jats:p>","DOI":"10.1111\/gtc.12500","type":"journal-article","created":{"date-parts":[[2017,5,10]],"date-time":"2017-05-10T03:46:39Z","timestamp":1494387999000},"page":"662-669","source":"Crossref","is-referenced-by-count":11,"title":["Neuron\u2010specific knockdown of the <i>Drosophila fat<\/i> induces reduction of life span, deficient locomotive ability, shortening of motoneuron terminal branches and defects in axonal targeting"],"prefix":"10.1111","volume":"22","author":[{"given":"Aya","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Applied Biology Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"},{"name":"The Center for Advanced Insect Research Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Applied Biology Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"},{"name":"The Center for Advanced Insect Research Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazushige","family":"Morishita","sequence":"additional","affiliation":[{"name":"Department of Applied Biology Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"},{"name":"The Center for Advanced Insect Research Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Applied Biology Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"},{"name":"The Center for Advanced Insect Research Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima City Kagoshima 890\u20108520 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima City Kagoshima 890\u20108520 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-9750","authenticated-orcid":false,"given":"Masamitsu","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Applied Biology Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"},{"name":"The Center for Advanced Insect Research Kyoto Institute of Technology Matsugasaki, Sakyo\u2010ku Kyoto 606\u20108585 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1456-y"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu055"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2765"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.12703\/P6-98"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.04.019"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320340429"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-016-0060-6"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2012.1669"},{"key":"e_1_2_6_10_1","first-page":"523","article-title":"Comparative integromics on FAT1, FAT2, FAT3 and FAT4","volume":"18","author":"Katoh Y.","year":"2006","journal-title":"Int. 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