All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3
All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3
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DOI：
10.1016/s1534-5807(03)00394-0
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发表时间：
2004-01-01
影响因子：
11.8
通讯作者：
Joyner, AL
中科院分区：
文献类型：
--
作者：
Bai, CB;Stephen, D;Joyner, AL
一个重要的问题是细胞如何在Gli转录因子水平上解释Hedgehog的梯度。Gli活性的全部范围及其对Hh的依赖性尚未确定，尽管Gli2激活剂和Gli3阻遏物已被牵连。使用脊髓作为模型系统，我们证明了Gli3可以作为激活剂抑制Hedgehog信号。Hh靶基因Gli1的所有表达都依赖于Gli2和Gli3。然而，与Gli2不同，Gli3需要内源性Gli1来诱导底板和V3中间神经元。引人注目的是，缺乏所有Gli功能的胚胎发育出运动神经元和三种腹侧中间神经元亚型，类似于缺乏Hh信号传导和Gli3的胚胎。因此，在脊髓中，所有Hh信号传导都是Gli依赖性的。此外，需要Gli 2和Gli 3的组合来调节运动神经元的发育和腹侧脊髓祖细胞的空间模式。
An important question is how the gradient of Hedgehog is interpreted by cells at the level of the Gli transcription factors. The full range of Gli activity and its dependence on Hh have not been determined, although the Gli2 activator and Gli3 repressor have been implicated. Using the spinal cord as a model system, we demonstrate that Gli3 can transduce Hedgehog signaling as an activator. All expression of the Hh target gene Gli1 is dependent on both Gli2 and Gli3. Unlike Gli2, however, Gli3 requires endogenous Gli1 for induction of floor plate and V3 interneurons. Strikingly, embryos lacking all Gli function develop motor neurons and three ventral interneuron subtypes, similar to embryos lacking Hh signaling and Gli3. Therefore, in the spinal cord all Hh signaling is Gli dependent. Furthermore, a combination of Gli2 and Gli3 is required to regulate motor neuron development and spatial patterning of ventral spinal cord progenitors.