Chemokine receptor CXCR7 non-cell-autonomously controls pontine neuronal migration and nucleus formation

Chemokine receptor CXCR7 non-cell-autonomously controls pontine neuronal migration and nucleus formation
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趋化因子受体CXCR7非细胞自主控制脑桥神经元迁移和细胞核形成

DOI:
10.1038/s41598-020-68852-z
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发表时间:
2020
期刊:
影响因子:
4.6
通讯作者:
Murakami Fujio
Murakami Fujio
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhu Yan;Hirata Tatsumi;Mackay Fabienne;Murakami Fujio

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长距离切向迁移将神经元从其诞生地运送到遥远的目的地,并将其纳入神经元回路。在这些长途旅行中,神经元迁移是如何被引导的,目前还没有完全了解。我们通过研究小鼠后脑脑桥核(PN)神经元的迁移来解决这一问题。PN神经元先从下菱形唇向前迁移,然后在三叉神经节根附近向腹侧迁移,向后脑前腹侧迁移。先前我们发现,在趋化因子受体CXCR4或其配体CXCL12缺失的小鼠中,PN神经元在后定位位置进行前向腹侧转向。然而,时空控制前向腹侧转向的机制尚不清楚。此外,CXCL12的非典型受体CXCR7在脑桥迁移中的作用还有待研究。在这里,我们发现在Cxcr7基因敲除中,由于前向腹侧转向位置变宽,PN被拉长。Cxcr7在PN神经元向目的地的迁移路线中不表达,但在脑膜中强烈表达。神经上皮特异性敲除Cxcr7并不能重现Cxcr7敲除中的PN表型,这表明Cxcr7可能从脑膜起非细胞自主作用。我们进一步表明,CXCR7通过调节CXCL12蛋白水平来调节脑桥迁移。
Long distance tangential migration transports neurons from their birth places to distant destinations to be incorporated into neuronal circuits. How neuronal migration is guided during these long journeys is still not fully understood. We address this issue by studying the migration of pontine nucleus (PN) neurons in the mouse hindbrain. PN neurons migrate from the lower rhombic lip first anteriorly and then turn ventrally near the trigeminal ganglion root towards the anterior ventral hindbrain. Previously we showed that in mouse depleted of chemokine receptor CXCR4 or its ligand CXCL12, PN neurons make their anterior-to-ventral turn at posteriorized positions. However, the mechanism that spatiotemporally controls the anterior-to-ventral turning is still unclear. Furthermore, the role of CXCR7, the atypical receptor of CXCL12, in pontine migration has yet to be examined. Here, we find that the PN is elongated in Cxcr7 knockout due to a broadened anterior-to-ventral turning positions. Cxcr7 is not expressed in migrating PN neuronsen routeto their destinations, but is strongly expressed in the pial meninges. Neuroepithelium-specific knockout of Cxcr7 does not recapitulate the PN phenotype in Cxcr7 knockout, suggesting that CXCR7 acts non-cell-autonomously possibly from the pial meninges. We show further that CXCR7 regulates pontine migration by modulating CXCL12 protein levels.
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发表时间: 2018-01-01
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