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IGF-1 受体调节大脑皮层迁移过程中神经元极性的动态变化。

IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration.

机构信息

Departamento de Química Biológica-CIQUIBIC, Fac.de Ciencias Químicas, Universidad Nacional de Córdoba, CONICET, Córdoba, X5000HUA, Córdoba, Argentina.

Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, CSIC (CNB-CSIC), Darwin 3, Campus de Cantoblanco, Madrid, 28049, Spain.

出版信息

Sci Rep. 2017 Aug 9;7(1):7703. doi: 10.1038/s41598-017-08140-5.

DOI:10.1038/s41598-017-08140-5
PMID:28794445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5550468/
Abstract

During cortical development, neurons undergo polarization, oriented migration and layer-type differentiation. The biological and biochemical mechanisms underlying these processes are not completely understood. In neurons in culture we showed that IGF-1 receptor activation is important for growth cone assembly and axonal formation. However, the possible roles of the insulin like growth factor-1 receptor (IGF-1R) on neuronal differentiation and polarization in vivo in mammals have not yet been studied. Using in utero electroporation, we show here that the IGF-1R is essential for neocortical development. Neurons electroporated with a shRNA targeting IGF-1 receptor failed to migrate to the upper cortical layers and accumulated at the ventricular/subventricular zones. Co-electroporation with a constitutively active form of PI3K rescued migration. The change of the morphology from multipolar to bipolar cells was also attenuated. Cells lacking the IGF-1 receptor remain arrested as multipolar forming a highly disorganized tissue. The typical orientation of the migrating neurons with the Golgi complex oriented toward the cortical upper layers was also affected by electroporation with shRNA targeting IGF-1 receptor. Finally, cells electroporated with the shRNA targeting IGF-1 receptor were unable to form an axon and, therefore, neuron polarity was absent.

摘要

在皮质发育过程中，神经元经历极化、定向迁移和层型分化。这些过程的生物学和生化机制尚不完全清楚。在培养的神经元中，我们表明 IGF-1 受体的激活对于生长锥的组装和轴突的形成很重要。然而，胰岛素样生长因子-1 受体 (IGF-1R) 在哺乳动物体内对神经元分化和极化的可能作用尚未得到研究。本文通过在体电穿孔实验表明，IGF-1R 对于新皮质的发育是必需的。用靶向 IGF-1 受体的 shRNA 电穿孔的神经元未能迁移到皮质上层，并积累在脑室/室下区。共转染组成型激活的 PI3K 可挽救迁移。从多极细胞向双极细胞的形态变化也减弱了。缺乏 IGF-1 受体的细胞仍然停滞在多极状态，形成高度紊乱的组织。用靶向 IGF-1 受体的 shRNA 电穿孔也会影响具有朝向皮质上层的高尔基复合体的迁移神经元的典型取向。最后，用靶向 IGF-1 受体的 shRNA 电穿孔的细胞不能形成轴突，因此不存在神经元极性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c18/5550468/06e6bd54ab27/41598_2017_8140_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c18/5550468/06e6bd54ab27/41598_2017_8140_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c18/5550468/a595d447d894/41598_2017_8140_Fig1_HTML.jpg
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