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Zebrafish hhex null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1

Ce Gao, Weidong Huang, Yuqi Gao, Ji Jan Lo, Lingfei Luo, Honghui Huang, Jun Chen, View ORCID ProfileJinrong Peng
doi: https://doi.org/10.1101/343517
Ce Gao
1MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China 310058
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Weidong Huang
1MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China 310058
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Yuqi Gao
1MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China 310058
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Ji Jan Lo
1MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China 310058
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Lingfei Luo
2College of Life Sciences, Southwest University, Chongqing, China
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Honghui Huang
2College of Life Sciences, Southwest University, Chongqing, China
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Jun Chen
3College of Life Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China 310058
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Jinrong Peng
1MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China 310058
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  • ORCID record for Jinrong Peng
  • For correspondence: pengjr@zju.edu.cn
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ABSTRACT

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 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 were expressed ectopically in the intrahepatic intestinal tube and knockdown of cdx1b and pdx1 restored the expression of sox9b in the mutant. Chromatin-immunoprecipitation analysis shows that Hhex binds to the promoters of pdx1 and cdx1b genes to repress their expression. We therefore propose that Hhex, Cdx1b and Pdx1 form a genetic network governing the patterning and morphogenesis of the HPD and digestive tract systems in zebrafish.

Abbreviations
Cdx1b
caudal-related homeobox 1b
ChIP
Chromatin-immunoprecipitation
HBPD
hepatobiliary and hepatopancreatic duct
Hhex
haematopoietically expressed homeobox
Pdx1
pancreatic and duodenal homeobox 1
WISH
whole-mount in situ hybridization
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Posted June 09, 2018.
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Zebrafish hhex null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1
Ce Gao, Weidong Huang, Yuqi Gao, Ji Jan Lo, Lingfei Luo, Honghui Huang, Jun Chen, Jinrong Peng
bioRxiv 343517; doi: https://doi.org/10.1101/343517
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Zebrafish hhex null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1
Ce Gao, Weidong Huang, Yuqi Gao, Ji Jan Lo, Lingfei Luo, Honghui Huang, Jun Chen, Jinrong Peng
bioRxiv 343517; doi: https://doi.org/10.1101/343517

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