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正确设置黑质需要 Reelin 介导的多巴胺能神经元快速、横向定向迁移。

Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons.

机构信息

Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany.

Institute of Reconstructive Neurobiology, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany.

出版信息

Elife. 2019 Jan 28;8:e41623. doi: 10.7554/eLife.41623.

DOI:10.7554/eLife.41623
PMID:30689541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6349407/
Abstract

Midbrain dopaminergic (mDA) neurons migrate to form the laterally-located substantia nigra pars compacta (SN) and medially-located ventral tegmental area (VTA), but little is known about the underlying cellular and molecular processes. Here we visualize the dynamic cell morphologies of tangentially migrating SN-mDA neurons in 3D and identify two distinct migration modes. Slow migration is the default mode in SN-mDA neurons, while fast, laterally-directed migration occurs infrequently and is strongly associated with bipolar cell morphology. Tangential migration of SN-mDA neurons is altered in absence of Reelin signaling, but it is unclear whether Reelin acts directly on migrating SN-mDA neurons and how it affects their cell morphology and migratory behavior. By specifically inactivating Reelin signaling in mDA neurons we demonstrate its direct role in SN-mDA tangential migration. Reelin promotes laterally-biased movements in mDA neurons during their slow migration mode, stabilizes leading process morphology and increases the probability of fast, laterally-directed migration.

摘要

中脑多巴胺能（mDA）神经元迁移形成外侧的黑质致密部（SN）和内侧的腹侧被盖区（VTA），但对于潜在的细胞和分子过程知之甚少。在这里，我们在 3D 中可视化了横向迁移的 SN-mDA 神经元的动态细胞形态，并确定了两种不同的迁移模式。缓慢迁移是 SN-mDA 神经元的默认模式，而快速的、侧向定向的迁移则很少发生，并且与双极细胞形态密切相关。Reelin 信号缺失会改变 SN-mDA 神经元的横向迁移，但不清楚 Reelin 是否直接作用于迁移中的 SN-mDA 神经元，以及它如何影响它们的细胞形态和迁移行为。通过特异性地在 mDA 神经元中失活 Reelin 信号，我们证明了它在 SN-mDA 横向迁移中的直接作用。Reelin 在 mDA 神经元的缓慢迁移模式中促进侧向运动，稳定前导过程形态，并增加快速侧向定向迁移的概率。

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