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

作     者：Qingxia Jin Yuqi Gao Shimin Shuai Yayue Chen Kaiyuan Wang Jun Chen Jinrong Peng Ce Gao Qingxia Jin;Yuqi Gao;Shimin Shuai;Yayue Chen;Kaiyuan Wang;Jun Chen;Jinrong Peng;Ce Gao

作者机构：College of Animal SciencesZhejiang UniversityHangzhouZhejiang 310058China Department of Human Cell Biology and GeneticsSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong 518055China College of Life SciencesZhejiang UniversityHangzhouZhejiang 310058China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2022年第49卷第12期

页      面：1101-1113页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by Centre for Computational Science and Engineering(CCSE)at Southern University of Science and Technology supported by the National Key R&D Program of China(2018YFA0800502) the National Natural Science Foundation of China(31900579,31830113)。 

主　　题：Cdx1b CDX2 Hhex Intestine development Liver development Prox1a Zebrafish 

摘      要：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(sc RNA-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.