A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of Sonic hedgehog in the neural tube
A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of Sonic hedgehog in the neural tube
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DOI：
10.1016/s1097-2765(01)00271-4
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发表时间：
2001-06-01
期刊：
影响因子：
16
通讯作者：
Struhl, G
中科院分区：
文献类型：
--
作者：
Briscoe, J;Chen, Y;Struhl, G
腹侧神经管中的细胞模式由底板细胞分泌的Sonic hedgehog（Shh）组织。为了测定直接Shh作用的范围，我们开发了一种通过Hh受体Patched（Ptc）的缺失形式（称为Ptc（Delta loop2））的异位表达来阻断Hedgehog（Hh）信号转导的一般方法。我们在果蝇中验证了这种方法，并使用小鼠Ptc（Delta loop2）（mPtc1（Delta loop2））阻断小鸡神经管中的Shh转导。mPtc1（Delta loop2）的表达引起细胞自主的腹到背开关的祖细胞身份和神经元的命运在整个腹侧神经管，支持梯度机制，使Shh的行为直接和在长距离。mPtc1（Delta looP2）表达也导致Shh向更多背侧细胞的异常扩散，表明Shh在神经管中，就像果蝇中的Hh一样，诱导了一种限制其作用范围的反馈机制。
Cell pattern in the ventral neural tube is organized by Sonic hedgehog (Shh) secreted by floor plate cells. To assay the range of direct Shh action, we developed a general method for blocking transduction of Hedgehog (Hh) signals through ectopic expression of a deleted form of the Hh receptor Patched (Ptc), termed Ptc(Delta loop2). We validated this method in Drosophila and used mouse Ptc(Delta loop2) (mPtc1(Delta loop2)) to block Shh transduction in the chick neural tube. mPtc1(Delta loop2) expression caused cell-autonomous ventral-to-dorsal switches in progenitor identity and neuronal fate throughout the ventral neural tube, supporting a gradient mechanism whereby Shh acts directly and at long range. mPtc1(Delta looP2) expression also caused the abnormal spread of Shh to more dorsal cells, indicating that Shh in the neural tube, like Hh in Drosophila, induces a feedback mechanism that limits its range of action.