{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:13:07Z","timestamp":1780481587901,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009287","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000}}],"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Huntington\u2019s disease is a progressive autosomal dominant neurodegenerative disorder caused by the expansion of a polyglutamine tract at the N-terminus of a large cytoplasmic protein. The\n                    <jats:italic>Drosophila huntingtin<\/jats:italic>\n                    (\n                    <jats:italic>htt<\/jats:italic>\n                    ) gene is widely expressed during all developmental stages from embryos to adults. However,\n                    <jats:italic>Drosophila htt<\/jats:italic>\n                    mutant individuals are viable with no obvious developmental defects. We asked if such defects could be detected in\n                    <jats:italic>htt<\/jats:italic>\n                    mutants in a background that had been genetically sensitized to reveal cryptic developmental functions. Amyloid precursor protein (APP) is linked to Alzheimer\u2019s disease. Appl is the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    APP ortholog and\n                    <jats:italic>Appl<\/jats:italic>\n                    signaling modulates axon outgrowth in the mushroom bodies (MBs), the learning and memory center in the fly, in part by recruiting Abl tyrosine kinase. Here, we find that\n                    <jats:italic>htt<\/jats:italic>\n                    mutations suppress axon outgrowth defects of \u03b1\u03b2 neurons in\n                    <jats:italic>Appl<\/jats:italic>\n                    mutant MB by derepressing the activity of Abl. We show that\n                    <jats:italic>Abl<\/jats:italic>\n                    is required in MB \u03b1\u03b2 neurons for their axon outgrowth. Importantly, both\n                    <jats:italic>Abl<\/jats:italic>\n                    overexpression and lack of expression produce similar phenotypes in the MBs, indicating the necessity of tightly regulating Abl activity. We find that Htt behaves genetically as a repressor of Abl activity, and consistent with this,\n                    <jats:italic>in vivo<\/jats:italic>\n                    FRET-based measurements reveal a significant increase in Abl kinase activity in the MBs when Htt levels are reduced. Thus, Appl and Htt have essential but opposing roles in MB development, promoting and suppressing Abl kinase activity, respectively, to maintain the appropriate intermediate level necessary for axon growth.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009287","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T13:47:02Z","timestamp":1611064022000},"page":"e1009287","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Htt is a repressor of Abl activity required for APP-induced axonal growth"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1795-2860","authenticated-orcid":true,"given":"Claire","family":"Marquilly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-563X","authenticated-orcid":true,"given":"Germain 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