The liver is a key endoderm-derived multifunctional organ within the digestive system.Prospero homeobox 1(Prox1)is an essential transcription factor for liver development,but its specific function is not well understo...The liver is a key endoderm-derived multifunctional organ within the digestive system.Prospero homeobox 1(Prox1)is an essential transcription factor for liver development,but its specific function is not well understood.Here,we show that hepatic development,including the formation of intrahepatic biliary and vascular networks,is severely disrupted in prox1a mutant zebrafish.We find that Prox1a is essential for liver growth and proper differentiation but not required for early hepatic cell fate specification.Intriguingly,prox1a depletion leads to ectopic initiation of a Cdx1b-mediated intestinal program and the formation of intestinal lumen-like structures within the liver.Morpholino knockdown of cdx1b alleviates liver defects in the prox1a mutant zebrafish.Finally,chromatin immunoprecipitation analysis reveals that Prox1a binds directly to the promoter region of cdx1b,thereby repressing its expression.Overall,our findings indicate that Prox1a is required to promote and protect hepatic development by repression of Cdx1b-mediated intestinal cell fate in zebrafish.展开更多
基金partially supported by grants from the National Key Research and Development Program of China and the National Natural Science Foundation of China(2018YFA0801000,32270889,2019YFA0802800,32070824,2015CB942800,2016YFA0100500,31871458,31671500,and 81371264)supported by Beijing Natural Science Foundation(5242009)a grant from the Fisheries Innovation Team of Beijing Agriculture Innovation Consortium(BAIC07-2023-02).
文摘The liver is a key endoderm-derived multifunctional organ within the digestive system.Prospero homeobox 1(Prox1)is an essential transcription factor for liver development,but its specific function is not well understood.Here,we show that hepatic development,including the formation of intrahepatic biliary and vascular networks,is severely disrupted in prox1a mutant zebrafish.We find that Prox1a is essential for liver growth and proper differentiation but not required for early hepatic cell fate specification.Intriguingly,prox1a depletion leads to ectopic initiation of a Cdx1b-mediated intestinal program and the formation of intestinal lumen-like structures within the liver.Morpholino knockdown of cdx1b alleviates liver defects in the prox1a mutant zebrafish.Finally,chromatin immunoprecipitation analysis reveals that Prox1a binds directly to the promoter region of cdx1b,thereby repressing its expression.Overall,our findings indicate that Prox1a is required to promote and protect hepatic development by repression of Cdx1b-mediated intestinal cell fate in zebrafish.
