Muncan Vanesa, Faro Ana, Haramis Anna-Pavlina G, Hurlstone Adam F L, Wienholds Erno, van Es Johan, Korving Jeroen, Begthel Harry, Zivkovic Danica, Clevers Hans
Netherlands Institute for Developmental Biology, Center for Biomedical Research, Hubrecht Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
EMBO Rep. 2007 Oct;8(10):966-73. doi: 10.1038/sj.embor.7401071. Epub 2007 Sep 7.
Previous studies have shown that Wnt signals, relayed through beta-catenin and T-cell factor 4 (Tcf4), are essential for the induction and maintenance of crypts in mice. We have now generated a tcf4 (tcf7l2) mutant zebrafish by reverse genetics. We first observe a phenotypic defect at 4 weeks post-fertilization (wpf), leading to death at about 6 wpf. The phenotype comprises a loss of proliferation at the base of the intestinal folds of the middle and distal parts of the intestine. The proximal intestine represents an independent compartment, as it expresses sox2 in the epithelium and barx1 in the surrounding mesenchyme, which are early stomach markers in higher vertebrates. Zebrafish are functionally stomach-less, but the proximal intestine might share its ontogeny with the mammalian stomach. Rare adult homozygous tcf4(-/-) 'escapers' show proliferation defects in the gut epithelium, but have no other obvious abnormalities. This study underscores the involvement of Tcf4 in maintaining proliferative self-renewal in the intestine throughout life.
先前的研究表明，通过β-连环蛋白和T细胞因子4（Tcf4）传递的Wnt信号对于小鼠隐窝的诱导和维持至关重要。我们现在通过反向遗传学方法构建了tcf4（tcf7l2）突变斑马鱼。我们首先在受精后4周（wpf）观察到表型缺陷，导致大约在6 wpf时死亡。该表型包括中肠和远端肠段肠褶底部增殖的丧失。近端肠代表一个独立的区域，因为它在上皮中表达sox2，在周围间充质中表达barx1，而sox2和barx1是高等脊椎动物早期胃的标志物。斑马鱼在功能上没有胃，但近端肠可能与哺乳动物的胃具有共同的个体发生过程。罕见的成年纯合tcf4（-/-）“存活者”在肠道上皮中表现出增殖缺陷，但没有其他明显异常。这项研究强调了Tcf4在整个生命过程中维持肠道增殖性自我更新的作用。
