PUBLICATION

Hepatocyte-specific Ablation in Zebrafish to Study Biliary-driven Liver Regeneration

Authors
Choi, T.Y., Khaliq, M., Ko, S., So, J., Shin, D.
ID
ZDB-PUB-150613-5
Date
2015
Source
Journal of visualized experiments : JoVE   (99): e52785 (Journal)
Registered Authors
Khaliq, Mehwish, Ko, Sungjin, Shin, Donghun, So, Juhoon
Keywords
none
MeSH Terms
  • Ablation Techniques/methods*
  • Animals
  • Animals, Genetically Modified
  • Biliary Tract/cytology
  • Biliary Tract/physiology*
  • Female
  • Hepatocytes/cytology*
  • Hepatocytes/drug effects
  • Liver/cytology
  • Liver/drug effects
  • Liver/physiology
  • Liver Regeneration/physiology*
  • Male
  • Metronidazole/pharmacology
  • Models, Animal
  • Nitroreductases/biosynthesis
  • Nitroreductases/genetics
  • Zebrafish
PubMed
26065829 Full text @ J. Vis. Exp.
Abstract
The liver has a great capacity to regenerate. Hepatocytes, the parenchymal cells of the liver, can regenerate in one of two ways: hepatocyte- or biliary-driven liver regeneration. In hepatocyte-driven liver regeneration, regenerating hepatocytes are derived from preexisting hepatocytes, whereas, in biliary-driven regeneration, regenerating hepatocytes are derived from biliary epithelial cells (BECs). For hepatocyte-driven liver regeneration, there are excellent rodent models that have significantly contributed to the current understanding of liver regeneration. However, no such rodent model exists for biliary-driven liver regeneration. We recently reported on a zebrafish liver injury model in which BECs extensively give rise to hepatocytes upon severe hepatocyte loss. In this model, hepatocytes are specifically ablated by a pharmacogenetic means. Here we present in detail the methods to ablate hepatocytes and to analyze the BEC-driven liver regeneration process. This hepatocyte-specific ablation model can be further used to discover the underlying molecular and cellular mechanisms of biliary-driven liver regeneration. Moreover, these methods can be applied to chemical screens to identify small molecules that augment or suppress liver regeneration.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping