{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:10:09Z","timestamp":1791688209760,"version":"4.3.4"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK124804"],"award-info":[{"award-number":["DK124804"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1942019"],"award-info":[{"award-number":["1942019"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glia resident within the entire gastrointestinal tract (GI). Overseeing essential GI functions such as gut motility and water balance, the ENS serves as a pivotal bidirectional link in the gut-brain axis. During early development, the ENS is primarily derived from enteric neural crest cells (ENCCs). Disruptions to ENCC development, as seen in conditions like Hirschsprung disease (HSCR), lead to the absence of ENS in the GI, particularly in the colon. In this study, using zebrafish, we devised an <jats:italic>in vivo<\/jats:italic> F0 CRISPR-based screen employing a robust, rapid pipeline integrating single-cell RNA sequencing, CRISPR reverse genetics, and high-content imaging. Our findings unveil various genes, including those encoding opioid receptors, as possible regulators of ENS establishment. In addition, we present evidence that suggests opioid receptor involvement in the neurochemical coding of the larval ENS. In summary, our work presents a novel, efficient CRISPR screen targeting ENS development, facilitating the discovery of previously unknown genes, and increasing knowledge of nervous system construction.<\/jats:p>","DOI":"10.1371\/journal.pone.0303914","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T17:25:48Z","timestamp":1717003548000},"page":"e0303914","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in establishment of the enteric nervous system"],"prefix":"10.1371","volume":"19","author":[{"given":"Rodrigo","family":"Moreno-Campos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen W.","family":"Singleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0427-4493","authenticated-orcid":true,"given":"Rosa A.","family":"Uribe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"pone.0303914.ref001","volume-title":"The Enteric Nervous System","author":"JB Furness","year":"2008"},{"key":"pone.0303914.ref002","doi-asserted-by":"crossref","first-page":"e8024171","DOI":"10.1155\/2020\/8024171","article-title":"The Enteric Nervous System and Its Emerging Role as a Therapeutic Target","volume":"2020","author":"MA Fleming","year":"2020","journal-title":"Gastroenterology Research and Practice"},{"key":"pone.0303914.ref003","doi-asserted-by":"crossref","first-page":"e13234","DOI":"10.1111\/nmo.13234","article-title":"The first brain: Species comparisons and evolutionary implications for the enteric and central nervous systems","volume":"30","author":"JB Furness","year":"2018","journal-title":"Neurogastroenterology & Motility"},{"key":"pone.0303914.ref004","article-title":"Enteric Nervous System: The Bridge Between the Gut Microbiota and Neurological Disorders","volume":"14","author":"Z-H Geng","year":"2022","journal-title":"Frontiers in Aging Neuroscience"},{"key":"pone.0303914.ref005","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1152\/physrev.00018.2022","article-title":"The enteric nervous system","volume":"103","author":"KA Sharkey","year":"2023","journal-title":"Physiological Reviews"},{"key":"pone.0303914.ref006","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1242\/dev.30.1.31","article-title":"The migration of neural crest cells to the wall of the digestive tract in avian embryo","volume":"30","author":"NML Douarin","year":"1973","journal-title":"Development"},{"key":"pone.0303914.ref007","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/aja.1002010307","article-title":"Mapping the origin of the avian enteric nervous system with a retroviral marker","volume":"201","author":"ML Epstein","year":"1994","journal-title":"Developmental Dynamics"},{"key":"pone.0303914.ref008","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.tig.2017.07.015","article-title":"Regulatory Logic Underlying Diversification of the Neural Crest","volume":"33","author":"ML Martik","year":"2017","journal-title":"Trends in Genetics"},{"key":"pone.0303914.ref009","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.semcdb.2017.01.006","article-title":"Enteric nervous system development: A crest cell\u2019s journey from neural tube to colon","volume":"66","author":"N Nagy","year":"2017","journal-title":"Seminars in Cell & Developmental Biology"},{"key":"pone.0303914.ref010","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/s41583-018-0041-0","article-title":"Enteric nervous system development: what could possibly go wrong?","volume":"19","author":"M Rao","year":"2018","journal-title":"Nat Rev Neurosci"},{"key":"pone.0303914.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-023-00465-y","article-title":"Hirschsprung disease","volume":"9","author":"L Montalva","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"pone.0303914.ref012","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ydbio.2016.07.008","article-title":"Genetics of enteric neuropathies","volume":"417","author":"E Brosens","year":"2016","journal-title":"Developmental Biology"},{"key":"pone.0303914.ref013","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s12276-021-00571-5","article-title":"Zebrafish as an animal model for biomedical research","volume":"53","author":"T-Y Choi","year":"2021","journal-title":"Exp Mol Med"},{"key":"pone.0303914.ref014","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/dvdy.24597","article-title":"Gut feelings: Studying enteric nervous system development, function, and disease in the zebrafish model system","volume":"247","author":"J. 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