PUBLICATION

Cdx1b protects intestinal cell fate by repressing signaling networks for liver specification

Authors
Jin, Q., Gao, Y., Shuai, S., Chen, Y., Wang, K., Chen, J., Peng, J., Gao, C.
ID
ZDB-PUB-221203-12
Date
2022
Source
Journal of genetics and genomics = Yi chuan xue bao   49(12): 1101-1113 (Journal)
Registered Authors
Chen, Jun, Peng, Jinrong
Keywords
CDX2, Cdx1b, Hhex, Prox1a, intestine development, liver development, zebrafish
MeSH Terms
  • Cell Differentiation*/genetics
  • Liver*/metabolism
  • Signal Transduction/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Mammals/metabolism
  • Intestines*/metabolism
  • Animals
  • Homeodomain Proteins*/genetics
  • Homeodomain Proteins*/metabolism
(all 12)
PubMed
36460297 Full text @ J. Genet. Genomics
Abstract
In mammals, the expression of the homeobox family member Cdx2/CDX2 is restricted within the intestine. Conditional ablation of the mouse Cdx2 in the endodermal cells causes a homeotic transformation of the intestine towards the esophagus or gastric fate. In this report, we show that null mutants of zebrafish cdx1b, encoding the counterpart of mammalian CDX2, could survive more than 10 days post fertilization, a stage when the zebrafish digestive system has been well developed. Through RNA sequencing (RNA-seq) and single cell sequencing (scRNA-seq) of the dissected intestine from the mutant embryos we demonstrated that the loss-of-function of the zebrafish cdx1b yields hepatocyte-like intestinal cells, a phenotype never observed in the mouse model. Further RNA-seq data analysis, genetic and signaling inhibitor studies reveal that Cdx1b functions to guard the intestinal fate by repressing, directly or indirectly, a range of transcriptional factors and signaling pathways for liver specification. Finally, we demonstrated that heatshock-induced overexpression of cdx1b in a transgenic fish abolishes the liver formation. Therefore, we demonstrate that Cdx1b is a key repressor of hepatic fate during the intestine specification in zebrafish.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zju25
    		Indel
    zju26
      		Small Deletion
      zju27
        		Small Deletion
        zju28TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          cdx1bCRISPR2-cdx1bCRISPR
          prox1aCRISPR1-prox1aCRISPR
          1 - 2 of 2
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          Fish
          No data available
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab-2F11monoclonalIgG1Mouse
          1 - 1 of 1
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          Orthology
          No data available
          Engineered Foreign Genes
          No data available
          Mapping
          No data available
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          Citation
          Jin, Q., Gao, Y., Shuai, S., Chen, Y., Wang, K., Chen, J., Peng, J., Gao, C. (2022) Cdx1b protects intestinal cell fate by repressing signaling networks for liver specification. Journal of genetics and genomics = Yi chuan xue bao. 49(12):1101-1113.