Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons
Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons
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DOI：
10.7554/elife.41623
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发表时间：
2019-01
期刊：
影响因子：
7.7
通讯作者：
A. R. Vaswani;Beatrice Weykopf;C. Hagemann;Hans-Ulrich Fried;O. Brüstle;S. Blaess
中科院分区：
文献类型：
--
作者：
A. R. Vaswani;Beatrice Weykopf;C. Hagemann;Hans-Ulrich Fried;O. Brüstle;S. Blaess
中脑多巴胺能（mDA）神经元迁移形成位于外侧的黑质致密部（SN）和位于内侧的腹侧被盖区（VTA），但人们对潜在的细胞和分子过程知之甚少。在这里，我们以 3D 形式可视化切向迁移 SN-mDA 神经元的动态细胞形态，并识别两种不同的迁移模式。慢速迁移是 SN-mDA 神经元的默认模式，而快速、横向定向迁移很少发生，并且与双极细胞形态密切相关。在没有 Reelin 信号传导的情况下，SN-mDA 神经元的切向迁移发生改变，但尚不清楚 Reelin 是否直接作用于迁移的 SN-mDA 神经元以及它如何影响其细胞形态和迁移行为。通过特异性灭活 mDA 神经元中的 Reelin 信号传导，我们证明了其在 SN-mDA 切向迁移中的直接作用。 Reelin 促进 mDA 神经元在缓慢迁移模式期间的横向偏向运动，稳定主导过程形态并增加快速、横向定向迁移的可能性。
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.