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

Jin, Qingxia1; Gao, Yuqi1; Shuai, Shimin2; Chen, Yayue1; Wang, Kaiyuan3; Chen, Jun3; Peng, Jinrong1; Gao, Ce1

2022-12-01

10.1016/j.jgg.2022.11.0061673-8527

Journal of Genetics and Genomics   影响因子和分区

1673-8527

1873-5533

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 demonstrate 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 demonstrate 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.Copyright (c) 2022, The Authors. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Cdx1b CDX2 Hhex Intestine development Liver development Prox1a Zebrafish

SCI

英语

其他

National Key R&D Program of China[2018YFA0800502] ; National Natural Science Foundation of China["31900579","31830113"]

Biochemistry & Molecular Biology ; Genetics & Heredity

Biochemistry & Molecular Biology ; Genetics & Heredity

WOS:000917286300001

SCIENCE PRESS

Web of Science

1.Zhejiang Univ, Coll Anim Sci, Hangzhou 310058, Zhejiang, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Dept Human Cell Biol & Genet, Shenzhen 518055, Guangdong, Peoples R China
3.Zhejiang Univ, Coll Life Sci, Hangzhou 310058, Zhejiang, Peoples R China

Jin, Qingxia,Gao, Yuqi,Shuai, Shimin,et al. Cdx1b protects intestinal cell fate by repressing signaling networks for liver specification[J]. Journal of Genetics and Genomics,2022,49(12).

Jin, Qingxia.,Gao, Yuqi.,Shuai, Shimin.,Chen, Yayue.,Wang, Kaiyuan.,...&Gao, Ce.(2022).Cdx1b protects intestinal cell fate by repressing signaling networks for liver specification.Journal of Genetics and Genomics,49(12).

Jin, Qingxia,et al."Cdx1b protects intestinal cell fate by repressing signaling networks for liver specification".Journal of Genetics and Genomics 49.12(2022).