{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:38:19Z","timestamp":1778571499568,"version":"3.51.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of China","doi-asserted-by":"publisher","award":["2015CB942802"],"award-info":[{"award-number":["2015CB942802"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of China","doi-asserted-by":"publisher","award":["2017YFA0504501"],"award-info":[{"award-number":["2017YFA0504501"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31330050"],"award-info":[{"award-number":["31330050"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571495"],"award-info":[{"award-number":["31571495"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The hepatopancreatic duct (HPD) system links the liver and pancreas to the intestinal tube and is composed of the extrahepatic biliary duct, gallbladder, and pancreatic duct. Haematopoietically expressed-homeobox (Hhex) protein plays an essential role in the establishment of HPD; however, the molecular mechanism remains elusive. Here, we show that zebrafish hhex-null mutants fail to develop the HPD system characterized by lacking the biliary marker Annexin A4 and the HPD marker sox9b. The hepatobiliary duct part of the mutant HPD system is replaced by an intrahepatic intestinal tube characterized by expressing the intestinal marker fatty acid-binding protein 2a (fabp2a). Cell lineage analysis showed that this intrahepatic intestinal tube is not originated from hepatocytes or cholangiocytes. Further analysis revealed that cdx1b and pdx1 are expressed ectopically in the intrahepatic intestinal tube and knockdown of cdx1b and pdx1 could restore the expression of sox9b in the mutant. Chromatin-immunoprecipitation analysis showed that Hhex binds to the promoters of pdx1 and cdx1b genes to repress their expression. We therefore propose that Hhex, Cdx1b, Pdx1, and Sox9b form a genetic network governing the patterning and morphogenesis of the HPD and digestive tract systems in zebrafish.<\/jats:p>","DOI":"10.1093\/jmcb\/mjy068","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T07:43:47Z","timestamp":1542095027000},"page":"448-462","source":"Crossref","is-referenced-by-count":31,"title":["Zebrafish hhex-null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1"],"prefix":"10.1093","volume":"11","author":[{"given":"Ce","family":"Gao","sequence":"first","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weidong","family":"Huang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqi","family":"Gao","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li Jan","family":"Lo","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingfei","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Southwest University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honghui","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Southwest University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinrong","family":"Peng","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,11,14]]},"reference":[{"key":"2019103107193432200_mjy068C1","doi-asserted-by":"crossref","first-page":"e0146806","DOI":"10.1371\/journal.pone.0146806","article-title":"Hhex is necessary for the hepatic differentiation of mouse ES cells and acts via Vegf signaling","volume":"11","author":"Arterbery","year":"2016","journal-title":"PLoS One"},{"key":"2019103107193432200_mjy068C2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.ymeth.2013.04.011","article-title":"The developmental epigenomics toolbox: ChIP-seq and MethylCap-seq profiling of early zebrafish embryos","volume":"62","author":"Bogdanovic","year":"2013","journal-title":"Methods"},{"key":"2019103107193432200_mjy068C3","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1028>3.0.CO;2-5","article-title":"Hex expression suggests a role in the development and function of organs derived from foregut endoderm","volume":"219","author":"Bogue","year":"2000","journal-title":"Dev. Dyn."},{"key":"2019103107193432200_mjy068C4","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1242\/dev.00965","article-title":"Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas","volume":"131","author":"Bort","year":"2004","journal-title":"Development"},{"key":"2019103107193432200_mjy068C5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ydbio.2005.11.006","article-title":"Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development","volume":"290","author":"Bort","year":"2006","journal-title":"Dev. 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