Ravanelli Andrew M, Kearns Christina A, Powers Rani K, Wang Yuying, Hines Jacob H, Donaldson Maranda J, Appel Bruce
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Dev Biol. 2018 Dec 15;444(2):93-106. doi: 10.1016/j.ydbio.2018.10.004. Epub 2018 Oct 19.
During development of the central nervous system oligodendrocyte precursor cells (OPCs) give rise to both myelinating oligodendrocytes and NG2 glia, which are the most proliferative cells in the adult mammalian brain. NG2 glia retain characteristics of OPCs, and some NG2 glia produce oligodendrocytes, but many others persist throughout adulthood. Why some OPCs differentiate as oligodendrocytes during development whereas others persist as OPCs and acquire characteristics of NG2 glia is not known. Using zebrafish spinal cord as a model, we found that OPCs that differentiate rapidly as oligodendrocytes and others that remain as OPCs arise in sequential waves from distinct neural progenitors. Additionally, oligodendrocyte and persistent OPC fates are specified during a defined critical period by small differences in Shh signaling and Notch activity, which modulates Shh signaling response. Thus, our data indicate that OPCs fated to produce oligodendrocytes or remain as OPCs during development are specified as distinct cell types, raising the possibility that the myelinating potential of OPCs is set by graded Shh signaling activity.
在中枢神经系统发育过程中，少突胶质前体细胞（OPCs）可分化为有髓鞘形成能力的少突胶质细胞和NG2胶质细胞，后者是成年哺乳动物大脑中增殖能力最强的细胞。NG2胶质细胞保留了少突胶质前体细胞的特征，一些NG2胶质细胞可产生少突胶质细胞，但其他许多细胞在成年期会持续存在。目前尚不清楚为何有些少突胶质前体细胞在发育过程中分化为少突胶质细胞，而另一些则作为少突胶质前体细胞持续存在并获得NG2胶质细胞的特征。我们以斑马鱼脊髓为模型，发现迅速分化为少突胶质细胞的少突胶质前体细胞和那些仍作为少突胶质前体细胞存在的细胞，是由不同的神经祖细胞按顺序依次产生的。此外，少突胶质细胞和持续存在的少突胶质前体细胞的命运，是在一个特定的关键时期，由Shh信号通路和Notch活性的微小差异决定的，Notch活性可调节Shh信号通路的反应。因此，我们的数据表明，在发育过程中注定要产生少突胶质细胞或仍作为少突胶质前体细胞存在的少突胶质前体细胞，被指定为不同的细胞类型，这增加了少突胶质前体细胞的髓鞘形成潜能由分级的Shh信号通路活性设定的可能性。
