Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1

Kirsten C. Sadler, Katherine N. Krahn, Naseem A. Gaur, Chinweike Ukomadu

Research output: Contribution to journalArticle

Abstract

In contrast to the deregulated hepatocellular division that is a feature of many hepatic diseases and malignancies, physiologic liver growth during embryonic development and after partial hepatectomy (PH) in adults is characterized by tightly controlled cell proliferation. We used forward genetic screening in zebrafish to test the hypothesis that a similar genetic program governs physiologic liver growth during hepatogenesis and regeneration after PH. We identified the uhrf1 gene, a cell cycle regulator and transcriptional activator of top2a expression, as required for hepatic outgrowth and embryonic survival. By developing a methodology to perform PH on adult zebrafish, we found that liver regeneration in uhrf1+/- adult animals is impaired. uhrf1 transcript levels dramatically increase after PH in both mice, and zebrafish and top2a is not up-regulated in uhrf1+/- livers after PH. This indicates that uhrf1 is required for physiologic liver growth in both embryos and adults and illustrates that zebrafish livers regenerate.

Original languageEnglish (US)
Pages (from-to)1570-1575
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number5
DOIs
StatePublished - Jan 30 2007

Keywords

  • Hepatic outgrowth
  • Hepatogenesis
  • Partial hepatectomy

ASJC Scopus subject areas

  • General

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