The newly identified migration inhibitory protein regulates the radial migration in the developing neocortex.
The newly identified migration inhibitory protein regulates the radial migration in the developing neocortex.
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DOI：
10.1038/srep05984
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发表时间：
2014-08-07
影响因子：
4.6
通讯作者：
Yamashita T
中科院分区：
文献类型：
--
作者：
Zhang S;Kanemitsu Y;Fujitani M;Yamashita T
神经元迁移是发育中的大脑皮层组织的关键过程。尽管已经确定了许多径向迁移的正向调节机制，但负向细胞自主机制尚未得到充分描述。在这里，我们报告了一种新发现的迁移抑制蛋白（MINP，以前称为 2900011O08Rik），它可以负向调节径向迁移。 MINP mRNA 在中枢和周围神经系统中特异性检测到，尤其在大脑皮层中富集。 MINP 免疫反应性与神经元标记 Tuj1 共定位，并在有丝分裂后神经元的细胞质中检测到。为了阐明 MINP 在发育中大脑中的功能，我们在子宫内将 MINP siRNA、MINP shRNA 或 MINP 过表达载体电穿孔到小鼠皮质中，并进行体内迁移测定。虽然 MINP 的敲低不会改变神经元形态，但发现 MINP 敲低会加速径向迁移，而 MINP 过表达会减少径向迁移。这种迁移表型也在体外得到证实，表明 MINP 以细胞自主的方式调节神经元迁移。此外，MINP 的下调通过与微管蛋白相互作用影响微管稳定性，微管蛋白是参与神经元迁移调节的潜在机制。
Neuronal migration is a crucial process in the organization of the developing cerebral cortex. Although a number of positive regulatory mechanisms of radial migration have been identified, negative cell-autonomous mechanisms have yet to be fully described. Here we report a newly identified Migration Inhibitory Protein (MINP, formerly known as 2900011O08Rik) that negatively regulates radial migration. MINP mRNA was specifically detected in the central and peripheral nervous system, and especially enriched in the cerebral cortex. MINP immunoreactivity co-localized with the neuronal marker Tuj1 and was detected in the cytoplasm of post-mitotic neurons. To elucidate the function of MINP in the developing brain, we performed in utero electroporation of MINP siRNA, MINP shRNA, or MINP-overexpressing vectors into mouse cortices and carried out in vivo migration assays. Whereas knockdown of MINP did not alter neuronal morphology, the radial migration was found accelerated by MINP knockdown, and reduced by MINP overexpression. This migration phenotype was also confirmed in vitro, indicating that MINP regulates neuronal migration in a cell-autonomous fashion. Furthermore, downregulation of MINP affected microtubule stability by interacting with tubulin that is a potential mechanism involved in the regulation of neuronal migration.