The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones
The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones
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DOI：
10.1016/j.celrep.2019.03.013
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发表时间：
2019-04-02
期刊：
影响因子：
8.8
通讯作者：
Kucenas, Sarah
中科院分区：
文献类型：
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作者：
Fontenas, Laura;Welsh, Taylor G.;Kucenas, Sarah
在发育过程中，少突胶质细胞祖细胞（OPCs）在整个脊髓中广泛迁移。然而，它们的迁移在过渡区受到限制。在这些专门的位置，独特的神经胶质细胞在斑马鱼和小鼠中发挥作用，防止外周OPC迁移，但这种调节的机制尚不清楚。为了阐明在运动出口点（MEP）TZs介导OPC分离的机制，我们进行了无偏的小分子筛选。使用化学筛选和体内成像，我们发现A2a腺苷受体（AR）的抑制导致OPC异位迁移出脊髓。我们提供了在体内的证据表明，神经调节，部分介导的腺苷，影响OPC迁移，特别是在MEP TZ。这项工作为了解OPCs在发育过程中如何到达其最终目的地开辟了令人兴奋的可能性，并确定了可能促进其在疾病中迁移的机制。
During development, oligodendrocyte progenitor cells (OPCs) migrate extensively throughout the spinal cord. However, their migration is restricted at transition zones (TZs). At these specialized locations, unique glial cells in both zebrafish and mice play a role in preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. To elucidate the mechanisms that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small-molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (ARs) causes ectopic OPC migration out of the spinal cord. We provide in vivo evidence that neuromodulation, partially mediated by adenosine, influences OPC migration specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease.