Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus.
Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus.
复制标题
后脑脉络丛的血管生长需要声波刺猬。
DOI：
10.1016/j.ydbio.2010.01.032
复制
发表时间：
2010
影响因子：
2.7
通讯作者：
Dymecki,SusanM
中科院分区：
文献类型：
--
作者：
Nielsen,CorinneM;Dymecki,SusanM
对脑脉络膜丛和肺等组织的交换和代谢功能至关重要的是与广泛的血管床紧密相关的大表面积上皮片的连贯发育。在此，我们在小鼠中进行了功能实验，证明由后脑脉络膜丛上皮产生的Sonic hedgehog基因（Shh）诱导了脉络膜丛功能基础的广泛血管生长和血管表面积，但不会诱导更专门的内皮细胞特征，如开窗和孔大小。我们的研究结果表明，即使在Vegf和其他血管生成因子存在的情况下，这些依赖于Shh的血管发育也会发生，这表明，在没有Shh的情况下，这些因子的水平不足，或者一组不同的因子可能对脉络膜丛的生长更为重要。传导Shh信号的是血管周围细胞——周细胞——而不是更完整的血管内皮细胞本身。此外，我们的研究结果表明，与其他血管内皮细胞相比，后脑脉络膜丛内皮细胞更依赖于周细胞的指导。因此，Shh除了作用于脉络膜丛上皮细胞的祖细胞外，还作用于脉络膜丛周细胞，并在协调两种不同但功能依赖的结构——脉络膜丛脉管系统及其鞘上皮的发育中起重要作用。
Critical to the exchange and metabolic functions served by tissues like brain choroid plexi and lung is the coherent development of an epithelial sheet of large surface area in tight apposition to an extensive vascular bed. Here, we present functional experiments in the mouse demonstrating that Sonic hedgehog (Shh) produced by hindbrain choroid plexus epithelium induces the extensive vascular outgrowths and vascular surface area fundamental to choroid plexus functions, but does not induce the more specialized endothelial cell features of fenestrations and bore size. Our findings indicate that these Shh-dependent vascular elaborations occur even in the presence of Vegf and other established angiogenic factors, suggesting either that the levels of these factors are inadequate in the absence of Shh or that a different set of factors may be more essential to choroid plexus outgrowth. Transducing the Shh signal is a perivascular cell—the pericyte—rather than the more integral vascular endothelial cell itself. Moreover, our findings suggest that hindbrain choroid plexus endothelial cells, as compared to other vascular endothelial cells, are more dependent upon pericytes for instruction. Thus, in addition to Shh acting on the progenitor pool for choroid plexus epithelial cells, as previously shown, it also acts on choroid plexus pericytes, and together serves the important role of coordinating the development of two disparate yet functionally dependent structures—the choroid plexus vasculature and its ensheathing epithelium.