{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:20:22Z","timestamp":1768461622559,"version":"3.49.0"},"reference-count":0,"publisher":"S. Karger AG","issue":"2-3","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells Tissues Organs"],"published-print":{"date-parts":[[2014]]},"abstract":"<b><i>Purpose:<\/i><\/b> The aim of this study was to determine the expression of <i>Cdx4 <\/i>(caudal-type homeobox gene-4) during anorectal development in normal and ethylenethiourea (ETU)-induced anorectal malformation (ARM) embryos with a view to establishing the possible role of <i>Cdx4 <\/i>in ARM pathogenesis. <b><i>Materials and Methods:<\/i><\/b> ARM was induced by ETU on the 10th gestational day (GD10) in rat embryos. Cesarean deliveries were then performed to harvest the embryos. Spatiotemporal expression of <i>Cdx4<\/i> was evaluated in normal rat embryos (n = 354) and ARM embryos (n = 378) from GD13 to GD16. <b><i>Results:<\/i><\/b> Immunohistochemical staining and immunofluorescence<b> <\/b>revealed that, in normal embryos, <i>Cdx4<\/i> expression was extensively detected on the epithelium of the cloaca on GD13. On GD14, the <i>Cdx4-<\/i>positive cells were intensively detected on the hindgut. On GD15, the anal membrane was constantly immunoreactive to <i>Cdx4.<\/i> On GD16, <i>Cdx4<\/i>-labeled cells were observed on the epithelium of the anus. In the ARM embryos, the epithelium of the cloaca, urorectal septum (URS) and anorectum was negative or faint for <i>Cdx4<\/i>. In the normal embryo group, <i>Cdx4<\/i> protein and mRNA expression showed time-dependent changes in the developing hindgut from GD13 to GD16 on Western blot and real-time reverse transcription plus polymerase chain reaction. Once the URS divided the cloaca into the primitive rectum and urogenital sinus (UGS) on GD15, <i>Cdx4<\/i> expression began to decrease. In addition, the expression level of <i>Cdx4<\/i> in the ARM group from GD13 to GD15 was significantly lower than that in the normal group (p < 0.05). <b><i>Conclusions:<\/i><\/b> In ARM embryos, an imbalance in the spatiotemporal expression of <i>Cdx4<\/i> was noted during anorectal morphogenesis from GD13 to GD16. This suggests that ETU may cause downregulation of <i>Cdx4<\/i> expression. Downregulation of <i>Cdx4<\/i> at the time of cloacal separation into the primitive rectum and UGS might thus be related to the development of ARM.<\/jats:p>","DOI":"10.1159\/000365965","type":"journal-article","created":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T07:29:49Z","timestamp":1416209389000},"page":"212-220","source":"Crossref","is-referenced-by-count":6,"title":["Spatiotemporal Expression of <b><i>Cdx4<\/i><\/b> in the Developing Anorectum of Rat Embryos with Ethylenethiourea-Induced Anorectal Malformations"],"prefix":"10.1159","volume":"199","author":[{"given":"Xiao Bing","family":"Tang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng Wei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Zuo","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2014,11,15]]},"container-title":["Cells Tissues Organs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/365965","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/365965","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:33:58Z","timestamp":1745429638000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000365965"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014]]},"references-count":0,"journal-issue":{"issue":"2-3","published-online":{"date-parts":[[2014,12,1]]},"published-print":{"date-parts":[[2014,12,15]]}},"URL":"https:\/\/doi.org\/10.1159\/000365965","archive":["Portico"],"relation":{},"ISSN":["1422-6405","1422-6421"],"issn-type":[{"value":"1422-6405","type":"print"},{"value":"1422-6421","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014]]}}}