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U.S.A."],"published-print":{"date-parts":[[2023,3,21]]},"abstract":"<jats:p>\n                    In the developmental remodeling of brain circuits, neurons are removed by glial phagocytosis to optimize adult behavior. Fragile X mental retardation protein (FMRP) regulates neuron-to-glia signaling to drive glial phagocytosis for targeted neuron pruning. We find that FMRP acts in a mothers against decapentaplegic (Mad)-insulin receptor (InR)-protein kinase B (Akt) pathway to regulate pretaporter (Prtp) and amyloid precursor protein-like (APPL) signals directing this glial clearance. Neuronal RNAi of\n                    <jats:italic>Drosophila fragile X mental retardation 1<\/jats:italic>\n                    (\n                    <jats:italic>dfmr1<\/jats:italic>\n                    ) elevates\n                    <jats:italic>mad<\/jats:italic>\n                    transcript levels and increases pMad signaling. Neuronal\n                    <jats:italic>dfmr1<\/jats:italic>\n                    and\n                    <jats:italic>mad<\/jats:italic>\n                    RNAi both elevate phospho\u2013protein kinase B (pAkt) and delay neuron removal but cause opposite effects on InR expression. Genetically correcting pAkt levels in the\n                    <jats:italic>mad<\/jats:italic>\n                    RNAi background restores normal remodeling. Consistently, neuronal\n                    <jats:italic>dfmr1<\/jats:italic>\n                    and\n                    <jats:italic>mad<\/jats:italic>\n                    RNAi both decrease Prtp levels, whereas neuronal\n                    <jats:italic>InR<\/jats:italic>\n                    and\n                    <jats:italic>akt<\/jats:italic>\n                    RNAi increase Prtp levels, indicating FMRP works with pMad and insulin signaling to tightly regulate Prtp signaling and thus control glial phagocytosis for correct circuit remodeling. Neuronal\n                    <jats:italic>dfmr1<\/jats:italic>\n                    and\n                    <jats:italic>mad<\/jats:italic>\n                    and\n                    <jats:italic>akt<\/jats:italic>\n                    RNAi all decrease APPL levels, with the pathway signaling higher glial endolysosome activity for phagocytosis. These findings reveal a FMRP-dependent control pathway for neuron-to-glia communication in neuronal pruning, identifying potential molecular mechanisms for devising fragile X syndrome treatments.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2216887120","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T13:39:52Z","timestamp":1678887592000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":15,"title":["Fragile X mental retardation protein coordinates neuron-to-glia communication for clearance of developmentally transient brain neurons"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4459-6929","authenticated-orcid":false,"given":"Chunzhu","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Vanderbilt University and Medical Center, Nashville, TN 37235"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendal","family":"Broadie","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Vanderbilt University and Medical Center, Nashville, TN 37235"},{"name":"Department of Cell and Developmental Biology, Vanderbilt University and Medical Center, Nashville, TN 37235"},{"name":"Kennedy Center for Research on Human Development, Vanderbilt University and Medical Center, Nashville, TN 37235"},{"name":"Vanderbilt Brain Institute, Vanderbilt University and Medical Center, Nashville, TN 37235"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202100254"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1660-20.2020"},{"key":"e_1_3_4_3_2","first-page":"197","article-title":"Neuronal and glial purinergic receptors functions in neuron development and brain disease","volume":"7","author":"del Puerto A.","year":"2013","unstructured":"A. del Puerto, F. 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