Evidence for a role of vertebrate Disp1 in long-range Shh signaling
Evidence for a role of vertebrate Disp1 in long-range Shh signaling
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DOI：
10.1242/dev.043547
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发表时间：
2010-01-01
期刊：
影响因子：
4.6
通讯作者：
Roelink, Henk
中科院分区：
文献类型：
--
作者：
Etheridge, L. Alton;Crawford, T. Quinn;Roelink, Henk
分派1 （Disp1）编码一个12个跨膜结构域蛋白，该蛋白是远程sonic hedgehog （Shh）信号传递所必需的。通过RNAi或显性阴性构建体抑制Disp1功能，可阻止分泌并导致源细胞中Shh的积累。测量来自胚胎干细胞（ES）的神经化胚样体（EBs）的Shh反应，无论是否具有Disp1功能，都证明了Disp1在运输Shh的细胞中的额外作用。与表达Shh的细胞共培养显示，在Disp1（-/-）神经化的EBs中，接触依赖性Shh反应的范围显着减少。这些观察结果支持Disp1的双重作用，不仅在源细胞中分泌Shh，而且在随后的组织中运输Shh。
Dispatched 1 (Disp1) encodes a twelve transmembrane domain protein that is required for long-range sonic hedgehog (Shh) signaling. Inhibition of Disp1 function, both by RNAi or dominant-negative constructs, prevents secretion and results in the accumulation of Shh in source cells. Measuring the Shh response in neuralized embryoid bodies (EBs) derived from embryonic stem (ES) cells, with or without Disp1 function, demonstrates an additional role for Disp1 in cells transporting Shh. Co-cultures with Shh-expressing cells revealed a significant reduction in the range of the contact-dependent Shh response in Disp1(-/-) neuralized EBs. These observations support a dual role for Disp1, not only in the secretion of Shh from the source cells, but also in the subsequent transport of Shh through tissue.