Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1
Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1
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DOI：
10.1073/pnas.0610774104
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发表时间：
2007-01-30
影响因子：
11.1
通讯作者：
Ukomadu, Chinweike
中科院分区：
文献类型：
--
作者：
Sadler, Kirsten C.;Krahn, Katherine N.;Ukomadu, Chinweike
与许多肝脏疾病和恶性肿瘤的特征肝细胞分裂不受控制相反，胚胎发育期间和成人部分肝切除术（PH）后的生理性肝脏生长的特点是细胞增殖受到严格控制。我们对斑马鱼进行了前向遗传筛选，以验证在ph后肝发生和再生过程中类似的遗传程序控制生理性肝脏生长的假设。我们发现了uhrf1基因，一种细胞周期调节因子和top2a表达的转录激活因子，是肝脏生长和胚胎存活所必需的。通过开发一种对成年斑马鱼进行PH的方法，我们发现uhrf1（+/-）成年动物的肝脏再生受到损害。两种小鼠的uhrf1转录物水平在PH后均显著升高，而斑马鱼的uhrf1（+/-）肝脏中，PH后uhrf1和top2a均未上调。这表明胚胎和成人的生生性肝脏生长都需要uhrf1，并说明斑马鱼的肝脏可以再生。
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.