Cervantes Sara, Yamaguchi Terry P, Hebrok Matthias
Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA.
Dev Biol. 2009 Feb 15;326(2):285-94. doi: 10.1016/j.ydbio.2008.11.020. Epub 2008 Dec 7.
Morphogenesis of the mammalian small intestine entails extensive elongation and folding of the primitive gut into a tightly coiled digestive tube. Surprisingly, little is known about the cellular and molecular mechanisms that mediate the morphological aspects of small intestine formation. Here, we demonstrate that Wnt5a, a member of the Wnt family of secreted proteins, is essential for the development and elongation of the small intestine from the midgut region. We found that the small intestine in mice lacking Wnt5a was dramatically shortened and duplicated, forming a bifurcated lumen instead of a single tube. In addition, cell proliferation was reduced and re-intercalation of post-mitotic cells into the elongating gut tube epithelium was disrupted. Thus, our study demonstrates that Wnt5a functions as a critical regulator of midgut formation and morphogenesis in mammals.
哺乳动物小肠的形态发生需要原始肠道广泛伸长并折叠成紧密盘绕的消化管。令人惊讶的是，对于介导小肠形成形态学方面的细胞和分子机制知之甚少。在此，我们证明Wnt5a（一种分泌蛋白Wnt家族的成员）对于中肠区域小肠的发育和伸长至关重要。我们发现，缺乏Wnt5a的小鼠小肠显著缩短并出现重复，形成双腔而不是单管。此外，细胞增殖减少，有丝分裂后细胞重新插入伸长的肠管上皮的过程受到破坏。因此，我们的研究表明Wnt5a在哺乳动物中肠形成和形态发生中起关键调节作用。
