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
-
- Animals
- Cell Differentiation*/genetics
- Homeodomain Proteins*/genetics
- Homeodomain Proteins*/metabolism
- Intestines*/metabolism
- Liver*/metabolism
- Mammals/metabolism
- Signal Transduction/genetics
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36460297 Full text @ J. Genet. Genomics
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping