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ZFIN ID: ZDB-PUB-090629-22
Compensatory growth mechanisms regulated by BMP and FGF signaling mediate liver regeneration in zebrafish after partial hepatectomy
Kan, N.G., Junghans, D., and Izpisúa Belmonte, J.C.
Date: 2009
Source: FASEB journal : official publication of the Federation of American Societies for Experimental Biology   23(10): 3516-3525 (Journal)
Registered Authors: Izpisúa Belmonte, Juan Carlos
Keywords: hepatocyte proliferation, liver-to-body weight ratio, liver mass restoration, Danio rerio
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Bone Morphogenetic Protein Receptors/genetics
  • Bone Morphogenetic Protein Receptors/physiology
  • Bone Morphogenetic Proteins/physiology*
  • Fibroblast Growth Factors/physiology*
  • Hepatectomy
  • Liver/growth & development
  • Liver/physiology*
  • Liver/surgery
  • Liver Regeneration*/genetics
  • Models, Animal
  • Organ Size
  • Receptor, Fibroblast Growth Factor, Type 1/genetics
  • Receptor, Fibroblast Growth Factor, Type 1/physiology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology*
PubMed: 19546304 Full text @ FASEB J.
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ABSTRACT
Here, we describe the zebrafish (Danio rerio) as a vertebrate model system to study liver regeneration with the added benefit of its powerful genetics and screening possibilities to uncover the molecular pathways underlying liver regeneration. We developed a partial hepatectomy (PH) protocol in zebrafish and investigated in detail the cellular and morphological changes during the process of liver regeneration. We show that the type of regenerative response is dependent on the size of the injury sustained by the zebrafish liver. Furthermore, we demonstrate for the first time that the mechanisms of liver regeneration in zebrafish after PH are strikingly similar to those of rodents and humans, with 100% recovery of the liver mass after 6-7 d postsurgery. This occurs via compensatory growth mediated by proliferation of hepatocytes throughout the entire liver remnant. By analyzing transgenic fish expressing dominant-negative forms of either bone morphogenetic protein (BMP) receptor or fibroblast growth factor (FGF) receptor 1, we demonstrate that the BMP and FGF signaling pathways are crucial regulators of the early events during liver regeneration after PH. Our study demonstrates that the mechanisms of liver regeneration in zebrafish are highly similar to the processes ongoing during mammalian liver regeneration and make the adult zebrafish a suitable model system to study the mechanisms of liver regeneration.-Kan, N. G., Junghans, D., Belmonte, J. C. I. Compensatory growth mechanisms regulated by BMP and FGF signaling mediate liver regeneration in zebrafish after partial hepatectomy.
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