Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22904, USA.
Cell Rep. 2019 Apr 2;27(1):115-128.e5. doi: 10.1016/j.celrep.2019.03.013.
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.
在发育过程中，少突胶质前体细胞（OPC）广泛迁移到整个脊髓中。然而，它们的迁移在过渡区（TZs）受到限制。在这些特殊的位置，斑马鱼和小鼠中的独特神经胶质细胞在防止外周 OPC 迁移中发挥作用，但这种调节的机制尚不清楚。为了阐明介导运动出口点（MEP）TZs 中 OPC 分离的机制，我们进行了一项无偏小分子筛选。使用化学筛选和体内成像，我们发现抑制 A2a 腺苷受体（ARs）会导致 OPC 异常迁移出脊髓。我们提供了体内证据，表明神经调节部分通过腺苷来影响 OPC 迁移，特别是在 MEP TZ 处。这项工作为理解 OPC 在发育过程中如何到达其最终目的地提供了令人兴奋的可能性，并确定了在疾病中促进其迁移的机制。
