Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice.
Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice.
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DOI：
10.1002/cne.23806
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发表时间：
2016-02-15
期刊：
影响因子：
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通讯作者：
Parnavelas JG
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作者：
Andrews WD;Davidson K;Tamamaki N;Ruhrberg C;Parnavelas JG
皮质中间神经元主要在内侧神经节隆起（MGE）中产生，并在发育中的皮质板内占据其最终位置之前通过端脑腹侧和背侧迁移。先前我们证明了来自Robo 1敲除（Robo 1 −/−）小鼠的中间神经元含有降低水平的神经纤毛蛋白1（Nrp 1）和丛蛋白A1受体，使得它们对纹状体中表达的脑信号蛋白配体的化学排斥作用的反应较低，并影响它们的迁移过程（埃尔南德斯米兰达等人[2011] J. Neurosci. 31：6174-6187）。早期的研究已经强调了Nrp 1和Nrp 2在神经元迁移中的重要性，在这里，我们评估了PlexinA 1在这个过程中的作用。在E14.5和E18.5，我们观察到与野生型同窝小鼠相比，PlexinA 1 −/−小鼠皮质中表达中间神经元标记物Gad 67和Lhx 6的细胞显著较少。虽然细胞凋亡的水平是相似的突变体和控制前脑，增殖显着减少在前者。此外，PlexinA 1 −/−小鼠MGE中的祖细胞似乎与心室表面锚定不良，并显示出降低的粘附特性，这可能是观察到的增殖减少的原因。总之，我们的数据揭示了PlexinA 1在前脑发育中的新作用。J. Comp.神经元524：518-534，2016.© 2015作者比较神经病学杂志出版的威利期刊公司。
Cortical interneurons are generated predominantly in the medial ganglionic eminence (MGE) and migrate through the ventral and dorsal telencephalon before taking their final positions within the developing cortical plate. Previously we demonstrated that interneurons from Robo1 knockout (Robo1−/−) mice contain reduced levels of neuropilin 1 (Nrp1) and PlexinA1 receptors, rendering them less responsive to the chemorepulsive actions of semaphorin ligands expressed in the striatum and affecting their course of migration (Hernandez‐Miranda et al. [2011] J. Neurosci. 31:6174–6187). Earlier studies have highlighted the importance of Nrp1 and Nrp2 in interneuron migration, and here we assess the role of PlexinA1 in this process. We observed significantly fewer cells expressing the interneuron markers Gad67 and Lhx6 in the cortex of PlexinA1 −/− mice compared with wild‐type littermates at E14.5 and E18.5. Although the level of apoptosis was similar in the mutant and control forebrain, proliferation was significantly reduced in the former. Furthermore, progenitor cells in the MGE of PlexinA1 −/− mice appeared to be poorly anchored to the ventricular surface and showed reduced adhesive properties, which may account for the observed reduction in proliferation. Together our data uncover a novel role for PlexinA1 in forebrain development. J. Comp. Neurol. 524:518–534, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.