{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:49:56Z","timestamp":1791373796730,"version":"4.3.1"},"posted":{"date-parts":[[2026,10,2]]},"group-title":"Physiology","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Gastrointestinal dysfunction is a prominent feature of neurodevelopmental disorders and contributes significantly to visceral discomfort, but the specific etiology is unclear. In particular, it is unknown which cell types within central, autonomic or enteric nervous systems, gut muscle, epithelium or immune system are the principal drivers of gut dysfunction. We report that the\n                  <jats:italic>Mecp2<\/jats:italic>\n                  mouse model of Rett syndrome, a neurodevelopmental disorder with profound gut dysmotility, exhibits impaired whole gut transit times and constipation\n                  <jats:italic>in vivo<\/jats:italic>\n                  as well as striking alterations to propagating neurogenic contractions in\n                  <jats:italic>ex vivo<\/jats:italic>\n                  colons. Selective elimination of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  in neurons, but not glia or smooth muscle, recapitulates these dysmotility phenotypes. Bulk RNA sequencing of colonic external muscle, containing the myenteric compartment of the enteric nervous system, showed significant expression changes in specific neurochemical signaling pathways. Pharmacological modulation of one, the M1 acetylcholine receptor, modified the aberrant neurogenic contractile phenotype in mutant mice and reproduced it in wild-type mice. These results identify disruptions to neuronal muscarinic signaling in the enteric nervous system in a mouse model of Rett syndrome and provide an experimental strategy to identify translationally relevant cellular and molecular pathways underlying gastrointestinal dysmotility in neurodevelopmental disorders.\n                <\/jats:p>","DOI":"10.64898\/2026.09.29.755242","type":"posted-content","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:55:13Z","timestamp":1790960113000},"source":"Crossref","is-referenced-by-count":0,"title":["Neurogenic colonic motility patterns and gut transit disrupted in a mouse model of Rett Syndrome"],"prefix":"10.64898","author":[{"given":"Nicole M.","family":"Procacci","sequence":"first","affiliation":[{"name":"Dept of Physiology & Cell Biology, University of Nevada Reno School of Medicine, Reno, NV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmita","family":"Debnath","sequence":"additional","affiliation":[{"name":"Dept of Physiology & Cell Biology, University of Nevada Reno School of Medicine, Reno, NV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajib","family":"Das","sequence":"additional","affiliation":[{"name":"Dept of Physiology & Cell Biology, University of Nevada Reno School of Medicine, Reno, NV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emer Ni","family":"Bhraonain","sequence":"additional","affiliation":[{"name":"Dept of Physiology & Cell Biology, University of Nevada Reno School of Medicine, Reno, NV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A.","family":"Cobine","sequence":"additional","affiliation":[{"name":"Dept of Physiology & Cell Biology, University of Nevada Reno School of Medicine, Reno, NV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Gould","sequence":"additional","affiliation":[{"name":"Dept of Physiology & Cell Biology, University of Nevada Reno School of Medicine, Reno, NV"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100703550550000_2026.09.29.755242v1.1","first-page":"723","article-title":"Uber ein eigenartiges hirnatrophisches Syndrom bei Hyperammon\u00e4mie im Kindersalter","volume":"116","year":"1966","journal-title":"Wiener Medizinische Wochenschrift"},{"key":"2026100703550550000_2026.09.29.755242v1.2","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-023-02169-6"},{"key":"2026100703550550000_2026.09.29.755242v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-89525-8_9"},{"issue":"9","key":"2026100703550550000_2026.09.29.755242v1.4","doi-asserted-by":"crossref","first-page":"e37284","DOI":"10.1097\/MD.0000000000037284","article-title":"Causal effects of gut microbiota on autism spectrum disorder: A two-sample mendelian randomization study","volume":"103","year":"2024","journal-title":"Medicine (Baltimore"},{"key":"2026100703550550000_2026.09.29.755242v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.11.021"},{"key":"2026100703550550000_2026.09.29.755242v1.6","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2013"},{"key":"2026100703550550000_2026.09.29.755242v1.7","doi-asserted-by":"crossref","unstructured":"Spencer NJ , Hu H . 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