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

Kirsten Sadler Edepli, 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

    Fingerprint

    Liver Regeneration
    Zebrafish
    Cell Cycle
    Embryonic Structures
    Hepatectomy
    Liver
    Growth
    cdc Genes
    Genetic Testing
    Embryonic Development
    Regeneration
    Cell Proliferation

    Keywords

    • Hepatic outgrowth
    • Hepatogenesis
    • Partial hepatectomy

    ASJC Scopus subject areas

    • General

    Cite this

    Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1. / Sadler Edepli, Kirsten; Krahn, Katherine N.; Gaur, Naseem A.; Ukomadu, Chinweike.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 5, 30.01.2007, p. 1570-1575.

    Research output: Contribution to journalArticle

    Sadler Edepli, Kirsten ; Krahn, Katherine N. ; Gaur, Naseem A. ; Ukomadu, Chinweike. / Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 5. pp. 1570-1575.
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