1. Academic Validation
  2. Cdx1b protects intestinal cell fate by repressing signaling networks for liver specification

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

  • J Genet Genomics. 2022 Nov 29;S1673-8527(22)00250-8. doi: 10.1016/j.jgg.2022.11.006.
Qingxia Jin 1 Yuqi Gao 1 Shimin Shuai 2 Yayue Chen 1 Kaiyuan Wang 3 Jun Chen 3 Jinrong Peng 4 Ce Gao 5
Affiliations

Affiliations

  • 1 College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
  • 2 Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
  • 3 College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
  • 4 College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China. Electronic address: [email protected].
  • 5 College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China. Electronic address: [email protected].
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, and genetic double mutants 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 heat shock-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.

Keywords

CDX2; Cdx1b; Hhex; Intestine development; Liver development; Prox1a; Zebrafish.

Figures
Products