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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:p>\n                    Mutations in\n                    <jats:italic>MECP2<\/jats:italic>\n                    give rise to Rett syndrome (RTT), an X-linked neurodevelopmental disorder that results in broad cognitive impairments in females. While the exact etiology of RTT symptoms remains unknown, one possible explanation for its clinical presentation is that loss of\n                    <jats:italic>MECP2<\/jats:italic>\n                    causes miswiring of neural circuits due to defects in the brain\u2019s capacity to respond to changes in neuronal activity and sensory experience. Here, we show that MeCP2 is phosphorylated at four residues in the mouse brain (S86, S274, T308, and S421) in response to neuronal activity, and we generate a quadruple knock-in (QKI) mouse line in which all four activity-dependent sites are mutated to alanines to prevent phosphorylation. QKI mice do not display overt RTT phenotypes or detectable gene expression changes in two brain regions. However, electrophysiological recordings from the retinogeniculate synapse of QKI mice reveal that while synapse elimination is initially normal at P14, it is significantly compromised at P20. Notably, this phenotype is distinct from the synapse refinement defect previously reported for\n                    <jats:italic>Mecp2<\/jats:italic>\n                    null mice, where synapses initially refine but then regress after the third postnatal week. We thus propose a model in which activity-induced phosphorylation of MeCP2 is critical for the proper timing of retinogeniculate synapse maturation specifically during the early postnatal period.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2310344120","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T15:03:42Z","timestamp":1698073422000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4734-6298","authenticated-orcid":false,"given":"Christopher P.","family":"Tzeng","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-7811","authenticated-orcid":false,"given":"Tess","family":"Whitwam","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"},{"name":"Program in Neuroscience, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4402-1060","authenticated-orcid":false,"given":"Lisa D.","family":"Boxer","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmy","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Silberfeld","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Trowbridge","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Shamah","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0428-3215","authenticated-orcid":false,"given":"Eric C.","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Renthal","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, F.M. Kirby Neurobiology Center, Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1380-2160","authenticated-orcid":false,"given":"Michael E.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90610-O"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.001"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.08.018"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.07.005"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6000-11.2012"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0175-11.2012"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3077-12.2012"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(99)80011-7"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.31.060407.125533"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2275"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.05.001"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.03.001"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","unstructured":"W. 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Lister Global epigenomic reconfiguration during mammalian brain development. Science (80-.) 341 1237905-1\u20131237905\u201312 (2013)."},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00611-6"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00451.2014"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.12.006"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty895"},{"key":"e_1_3_4_60_2","doi-asserted-by":"crossref","unstructured":"C. P. Tzeng T. Whitwam L. D. Boxer M. E. Greenberg Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE245026. 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