{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:19:45Z","timestamp":1792531185109,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T00:00:00Z","timestamp":1526428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81170943"],"award-info":[{"award-number":["81170943"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7162053"],"award-info":[{"award-number":["7162053"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sonic hedgehog (\n                    <jats:italic>Shh<\/jats:italic>\n                    ) is crucial for organogenesis in the foregut. This study investigated the function of\n                    <jats:italic>Shh<\/jats:italic>\n                    at the late\u2010gestational stage; during which, the esophagus continues to differentiate. We established cytokeratin 14 (\n                    <jats:italic>CK14<\/jats:italic>\n                    )\n                    <jats:italic>\n                      \u2010Cre;Shh\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    mice in which the down\u2010regulation of\n                    <jats:italic>Shh<\/jats:italic>\n                    in the epithelium occurred at approximately the same time as esophageal muscle conversion. Hematoxylin and eosin and immunohistochemical staining, with antibodies against keratin 14, Shh, patched 1 (Ptch1), Gli1, proliferating cell nuclear antigen (PCNA), \u03b1\u2010smooth muscle actin (\u03b1SMA), high\u2010molecular\u2010weight caldesmon (hCD), myogenin, paired box 7 (Pax7), \u03b23\u2010tubulin, and protein gene product 9.5 (PGP9.5), was performed to detect specific tissue dysplasia. Organ culture was conducted\n                    <jats:italic>in vitro<\/jats:italic>\n                    , and total mRNA was extracted to determine the transcriptional dysregulation. The esophagus of\n                    <jats:italic>\n                      CK14\u2010Cre; Shh\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    mice developed into an independent tube with an obvious dilatation at postnatal d 0.5. The number of cell layers and the expression of PCNA were decreased in mutant mice, compared with those in wild\u2010type mice. The expression of hCD declined progressively in the middle, distal, and lower esophageal sphincter levels of the mutant esophagus from embryonic d 17.5, compared with the expression in wild\u2010type littermates. Pax7 accumulation and myogenin reduction in mutant mice indicated that esophageal skeletal\u2010myoblast progression was blocked. RNA sequencing analysis revealed a significant down\u2010regulation of genes involved in proliferation and muscular motivation in\n                    <jats:italic>\n                      CK14\u2010Cre;Shh\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Thus, loss of\n                    <jats:italic>Shh<\/jats:italic>\n                    at the late\u2010 gestational stage leads to megaesophagus with reduced proliferation and a muscle development disorder in mice. mice.\u2014Jia, X., Min, L., Zhu, S., Zhang, S., Huang, X. Loss of sonic hedgehog gene leads to muscle development disorder and megaesophagus in mice.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 5703\u20135715 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701581r","type":"journal-article","created":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T15:25:34Z","timestamp":1526484334000},"page":"5703-5715","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Loss of sonic hedgehog gene leads to muscle development disorder and megaesophagus in mice"],"prefix":"10.1096","volume":"32","author":[{"given":"Xueting","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Gastroenterology National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases"},{"name":"Department of Stomatology Beijing Friendship Hospital, Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengtao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shutian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Stomatology Beijing Friendship Hospital, Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000155225"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1029>3.0.CO;2-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.044586"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201301005"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.06.041"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31549"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200402054"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.009324"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.12.2763"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90627-3"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.05.010"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301141"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2003.50005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.12.2397"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/1711"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/1717"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.22.4775"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.04.042"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1172\/JCI66603","article-title":"Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett\u2019s metaplasia","volume":"124","author":"Wang D. 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