Sequential specification of oligodendrocyte lineage cells by distinct levels of Hedgehog and Notch signaling
Sequential specification of oligodendrocyte lineage cells by distinct levels of Hedgehog and Notch signaling
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DOI：
10.1016/j.ydbio.2018.10.004
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发表时间：
2018-12-15
影响因子：
2.7
通讯作者：
Appel, Bruce
中科院分区：
文献类型：
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作者：
Ravanelli, Andrew M.;Kearns, Christina A.;Appel, Bruce
在中枢神经系统发育过程中，少突胶质前体细胞（OPCs）产生髓鞘化少突胶质细胞和NG2胶质细胞，其是成年哺乳动物脑中最具增殖性的细胞。NG2胶质细胞保留了OPCs的特征，一些NG2胶质细胞产生少突胶质细胞，但许多其他胶质细胞在整个成年期持续存在。为什么一些OPCs在发育过程中分化为少突胶质细胞，而另一些OPCs持续存在并获得NG2胶质细胞的特征尚不清楚。使用斑马鱼脊髓作为模型，我们发现，OPCs，迅速分化为少突胶质细胞和其他人仍然作为OPCs出现在连续波从不同的神经祖细胞。此外，少突胶质细胞和持续性OPC的命运在一个定义的关键时期内指定的小差异Shh信号和Notch活性，调节Shh信号反应。因此，我们的数据表明，OPCs注定要产生少突胶质细胞或在发育过程中保持为OPCs被指定为不同的细胞类型，提高了OPCs的髓鞘形成潜力由分级Shh信号活性设定的可能性。
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.