Netrin-DCC Signaling Regulates Corpus Callosum Formation Through Attraction of Pioneering Axons and by Modulating Slit2-Mediated Repulsion
Netrin-DCC Signaling Regulates Corpus Callosum Formation Through Attraction of Pioneering Axons and by Modulating Slit2-Mediated Repulsion
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DOI：
10.1093/cercor/bhs395
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发表时间：
2014-05-01
期刊：
影响因子：
3.7
通讯作者：
Richards, Linda J.
中科院分区：
文献类型：
--
作者：
Fothergill, Thomas;Donahoo, Amber-Lee S.;Richards, Linda J.
神经系统的左侧和右侧通过连合轴突进行交流，这些轴突在发育过程中使用进化上保守的分子穿过中线。这些指导线索已经在哺乳动物脊髓中得到了很好的研究，但目前还不清楚连合轴突的这些指导机制是否在发育中的前脑中是相似的，特别是对于胼胝体，最大和最重要的连合皮质功能。在这里，我们表明，Netrin1最初吸引来自扣带皮层的胼胝体先驱轴突，但令人惊讶的是，没有吸引力的新皮层胼胝体轴突，使大部分的投影。相反，我们表明，Netrin在结直肠癌信号传导中以一种根本不同的方式起作用，以防止Slit2介导的交叉前轴突的排斥，从而使它们接近并穿过中线。这些结果提供了第一个证据，胼胝体轴突如何整合多种指导线索，以导航中线。
The left and right sides of the nervous system communicate via commissural axons that cross the midline during development using evolutionarily conserved molecules. These guidance cues have been particularly well studied in the mammalian spinal cord, but it remains unclear whether these guidance mechanisms for commissural axons are similar in the developing forebrain, in particular for the corpus callosum, the largest and most important commissure for cortical function. Here, we show that Netrin1 initially attracts callosal pioneering axons derived from the cingulate cortex, but surprisingly is not attractive for the neocortical callosal axons that make up the bulk of the projection. Instead, we show that Netrin-deleted in colorectal cancer signaling acts in a fundamentally different manner, to prevent the Slit2-mediated repulsion of precrossing axons thereby allowing them to approach and cross the midline. These results provide the first evidence for how callosal axons integrate multiple guidance cues to navigate the midline.