Temporally- and spatially regulated generation of distinct descendants by sonic hedgehog-expressing progenitors in the forebrain
Temporally- and spatially regulated generation of distinct descendants by sonic hedgehog-expressing progenitors in the forebrain
复制标题
前脑中表达声音刺猬的祖细胞在时间和空间上调节不同后代的产生
作者：
Wada Y;Yamauchi K;Murakami F;Tanabe Y
不同神经亚型的产生取决于脊椎动物CNS发育过程中细胞外在和内在因子的活动。以前的研究提供了一个分子基础，神经祖细胞是如何形成模式，并产生不同的后代，空间和时间的诱导信号分泌的极化源调节。然而，它仍然是未知的，位于诱导信号的极化源的祖细胞的神经后代的产生是如何控制的。Sonic hedgehog（Shh）在前脑腹侧中线表达，已被证明对前脑中不同神经亚型的模式化和规范化起关键作用。在这里，我们通过使用ShhcreERT 2小鼠驱动系分析了在前脑中离散时间点产生的Shh-后代的身份和分布，其中将他莫昔芬诱导的Cre盒与Z/EG小鼠报告系一起插入Shh基因座。我们的研究结果表明，表达Shh的神经前体细胞产生的神经元和胶质细胞后代以时间上不同的方式分布在整个端脑和间脑。此外，我们的研究结果表明，Shh祖细胞位于两个空间上不同的子域，其特征在于它们在时间上不同的Shh表达模式。这些结果表明，指定神经亚型的时间和空间控制机制在表达Shh的祖细胞结构域中起作用，并提出了Shh活性的不同时间梯度可能是端脑中不同神经亚型产生的原因。© 2010 Wiley Periodicals，Inc.开发神经生物学，2012年
The generation of distinct neural subtypes depends on the activities of cell‐extrinsic and ‐intrinsic factors during the development of the vertebrate CNS. Previous studies have provided a molecular basis for how neural progenitors are patterned and generate distinct descendants that are spatially and temporally regulated by inductive signals secreted by polarized sources. However, it still remains unknown how the generation of neural descendants by progenitors located at polarized sources of inductive signals is controlled. Sonic hedgehog (Shh), which is expressed at the ventral midline in the forebrain, has been shown to play a critical role for the patterning and specification of distinct neural subtypes in the forebrain. Here, we analyzed the identities and distributions ofShh‐descendants generated at discrete time points in the forebrain by using a ShhcreERT2mouse driver line in which a tamoxifen‐inducible Cre cassette was inserted into theShhlocus together with a Z/EG mouse reporter line. Our results showed thatShh‐expressing neural progenitors generated neuronal and glial descendants distributed throughout the telencephalon and diencephalon in a temporally distinct manner. Furthermore, our results showed that Shh‐progenitors are located at two spatially distinct sub‐domains that can be characterized by their temporally distinct patterns ofShhexpression. These results suggest that temporally‐ and spatially controlled mechanisms that specify neural subtypes operate in theShh‐expressing progenitor domain, and raise the possibility that the distinct temporal gradient of Shh activity might be responsible for the generation of distinct neural subtypes in the telencephalon. © 2010 Wiley Periodicals, Inc. Develop Neurobiol, 2012