{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T20:52:44Z","timestamp":1773262364604,"version":"3.50.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese National Key Research and Development Project","award":["2019YFA0802402"],"award-info":[{"award-number":["2019YFA0802402"]}]},{"name":"Chinese National Key Research and Development Projecr","award":["2018YFC1003203"],"award-info":[{"award-number":["2018YFC1003203"]}]},{"name":"National Scientific Foundation of China","award":["32050109"],"award-info":[{"award-number":["32050109"]}]},{"name":"National Scientific Foundation of China","award":["31970757"],"award-info":[{"award-number":["31970757"]}]},{"name":"National Scientific Foundation of China","award":["31900576"],"award-info":[{"award-number":["31900576"]}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    Feingold syndrome type 1, caused by loss-of-function of MYCN, is characterized by varied phenotypes including esophageal and duodenal atresia. However, no adequate model exists for studying the syndrome\u2019s pathological or molecular mechanisms, nor is there a treatment strategy. Here, we developed a zebrafish Feingold syndrome type 1 model with nonfunctional\n                    <jats:italic>mycn<\/jats:italic>\n                    , which had severe intestinal atresia. Single-cell RNA-seq identified a subcluster of intestinal cells that were highly sensitive to Mycn, and impaired cell proliferation decreased the overall number of intestinal cells in the\n                    <jats:italic>mycn<\/jats:italic>\n                    mutant fish. Bulk RNA-seq and metabolomic analysis showed that expression of ribosomal genes was down-regulated and that amino acid metabolism was abnormal. Northern blot and ribosomal profiling analysis showed abnormal rRNA processing and decreases in free 40S, 60S, and 80S ribosome particles, which led to impaired translation in the mutant. Besides, both Ribo-seq and western blot analysis showed that mTOR pathway was impaired in\n                    <jats:italic>mycn<\/jats:italic>\n                    mutant, and blocking mTOR pathway by rapamycin treatment can mimic the intestinal defect, and both L-leucine and Rheb, which can elevate translation via activating TOR pathway, could rescue the intestinal phenotype of\n                    <jats:italic>mycn<\/jats:italic>\n                    mutant. In summary, by this zebrafish Feingold syndrome type 1 model, we found that disturbance of ribosomal biogenesis and blockage of protein synthesis during development are primary causes of the intestinal defect in Feingold syndrome type 1. Importantly, our work suggests that leucine supplementation may be a feasible and easy treatment option for this disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3001856","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T13:21:57Z","timestamp":1667308917000},"page":"e3001856","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mycn regulates intestinal development through ribosomal biogenesis in a zebrafish model of Feingold syndrome 1"],"prefix":"10.1371","volume":"20","author":[{"given":"Yun-Fei","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Xin","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Mo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo-Qin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mao-Guang","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ding-Hao","family":"Zhuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Yi","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Zhi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Sheng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng-Fei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"pbio.3001856.ref001","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1038\/s41467-018-03788-7","article-title":"Distinct molecular pathways mediate Mycn and Myc-regulated miR-17-92 microRNA action in Feingold syndrome mouse models","volume":"9","author":"F Mirzamohammadi","year":"2018","journal-title":"Nat Commun"},{"key":"pbio.3001856.ref002","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1002\/ajmg.a.31407","article-title":"Expanding the clinical spectrum of MYCN-related Feingold syndrome","volume":"140","author":"A Teszas","year":"2006","journal-title":"Am J Med Genet A"},{"key":"pbio.3001856.ref003","doi-asserted-by":"crossref","first-page":"13726","DOI":"10.1073\/pnas.1610626113","article-title":"Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors","volume":"113","author":"MW Richards","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pbio.3001856.ref004","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1158\/1541-7786.MCR-13-0536","article-title":"The N-myc Oncogene: Maximizing its Targets, Regulation, and Therapeutic Potential","volume":"12","author":"H. 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