PUBLICATION
Hhex and Prox1a synergistically dictate the hepatoblast to hepatocyte differentiation in zebrafish
- Authors
- Jin, Q., Hu, Y., Gao, Y., Zheng, J., Chen, J., Gao, C., Peng, J.
- ID
- ZDB-PUB-231106-5
- Date
- 2023
- Source
- Biochemical and Biophysical Research Communications 686: 149182149182 (Journal)
- Registered Authors
- Chen, Jun, Peng, Jinrong
- Keywords
- Bmp signaling, Endoderm, Hepatoblast, Hhex, Liver development, Prox1, Zebrafish
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Hepatocytes
- Liver*
- Prospective Studies
- Repressor Proteins
- Zebrafish*/genetics
- Zebrafish Proteins/genetics
- PubMed
- 37922575 Full text @ Biochem. Biophys. Res. Commun.
Citation
Jin, Q., Hu, Y., Gao, Y., Zheng, J., Chen, J., Gao, C., Peng, J. (2023) Hhex and Prox1a synergistically dictate the hepatoblast to hepatocyte differentiation in zebrafish. Biochemical and Biophysical Research Communications. 686:149182149182.
Abstract
The specification of endoderm cells to prospective hepatoblasts is the starting point for hepatogenesis. However, how a prospective hepatoblast gains the hepatic fate remains elusive. Previous studies have shown that loss-of-function of either hhex or prox1a alone causes a small liver phenotype but without abolishing the hepatocyte differentiation, suggesting that absence of either Hhex or Prox1a alone is not sufficient to block the hepatoblast differentiation. Here, via genetic studies of the zebrafish two single (hhex-/- and prox1a-/-) and one double (hhex-/-prox1a-/-) mutants, we show that simultaneous loss-of-function of the hhex and prox1a two genes does not block the endoderm cells to gain the hepatoblast potency but abolishes the hepatic differentiation from the prospective hepatoblast. Consequently, the hhex-/-prox1a-/- double mutant displays a liverless phenotype that cannot be rescued by the injection of bmp2a mRNA. Taken together, we provide strong evidences showing that Hhex teams with Prox1a to act as a master control of the differentiation of the prospective hepatoblasts towards hepatocytes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping