We report here that Glypican-6 (GPC6)-null mice display at birth small intestines that are 75% shorter than those of normal littermates. Notably, we demonstrate that the role of GPC6 in intestinal elongation is mediated by both Hedgehog (Hh) and non-canonical Wnt signaling. Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction. Here we provide strong support to this hypothesis by showing that GPC6 binds to Ptc1 in the mesenchymal layer of embryonic intestines. This study also provides experimental evidence that strongly suggests that GPC6 inhibits the activity of Wnt5a on the intestinal epithelium by binding to this growth factor, and reducing its release from the surrounding mesenchymal cells. Finally, we show that whereas the mesenchymal layer of GPC6-null intestines displays reduced cell proliferation and a thinner smooth muscle layer, epithelial cell differentiation is not altered in the mutant gut.

中文翻译：

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Glypican-6通过同时调节刺猬和非经典Wnt信号传导来刺激肠道伸长。

我们在这里报告，Glypican-6（GPC6）-无效的小鼠在出生时显示的小肠比正常同窝仔的短75％。值得注意的是，我们证明了GPC6在小肠伸长中的作用是由Hedgehog（Hh）和非经典Wnt信号介导的。根据体外实验的结果，我们先前曾提出GPC6通过与Hh和Patched1（Ptc1）相互作用并促进/稳定它们的相互作用来刺激Hh信号传导。在这里，我们通过显示GPC6与胚胎小肠的间充质层中的Ptc1结合，为这一假设提供了有力的支持。这项研究还提供了实验证据，有力地表明，GPC6通过与该生长因子结合并减少其从周围间充质细胞的释放来抑制Wnt5a在肠道上皮中的活性。最后，