CNS Myelin Sheath Lengths Are an Intrinsic Property of Oligodendrocytes.
CNS Myelin Sheath Lengths Are an Intrinsic Property of Oligodendrocytes.
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DOI：
10.1016/j.cub.2015.07.056
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发表时间：
2015-09-21
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影响因子：
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通讯作者：
Ffrench-Constant C
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作者：
Bechler ME;Byrne L;Ffrench-Constant C
自近一个世纪前Río-Hortega对少突胶质细胞形态的描述以来，许多研究已经观察到中枢神经系统区域之间髓鞘鞘长度的差异。髓鞘长度通过影响Ranvier淋巴结间距直接影响轴突传导速度。这种差异可能会影响神经信号的协调和同步。髓鞘长度的区域差异的原因尚不清楚；髓鞘长度仅由轴突决定还是不同少突胶质前体细胞群的内在特性影响长度？普遍的观点是，轴突为少突胶质细胞髓鞘形成和适当的鞘长提供了必要的分子线索。这一观点是基于轴突直径与髓鞘长度相关的观察，以及PNS轴突神经调节蛋白1 III型调节雪旺细胞髓鞘的起始和性质的报道。然而，在中枢神经系统中，没有这样的指导性分子被证明是必需的，越来越多的体外证据支持少突胶质细胞驱动的、独立于神经元的分化和形成初始鞘的能力。我们测试了这个替代信号无关的假设，即节间长度的变化反映了区域少突胶质细胞的内在特性。利用微纤维，我们发现少突胶质细胞具有显著的自我调节能力，可以形成致密的多层髓鞘，并产生生理长度的鞘。我们的研究结果表明，少突胶质细胞对纤维直径有反应，脊髓少突胶质细胞在纤维、共培养和外植体上比皮质少突胶质细胞产生更长的鞘，这表明少突胶质细胞具有区域特征，并产生不同的鞘长度，这反映了体内的节间。少突胶质细胞，而不是雪旺细胞，在没有轴突信号的情况下形成髓鞘，少突胶质细胞感知直径，随着纤维变大而增加鞘长度，皮层和脊髓的少突胶质细胞形成不同长度的鞘，鞘长度的区域差异最初可能是硬连接的，哺乳动物大脑的大部分由髓鞘包裹的轴突组成，其长度决定了传导速度。Bechler等人推翻了长期以来认为形成鞘的少突胶质细胞都是相同的观点。来自不同区域的少突胶质细胞在微纤维和神经元上产生鞘长度，这反映了它们在体内的起源。
Since Río-Hortega’s description of oligodendrocyte morphologies nearly a century ago, many studies have observed myelin sheath-length diversity between CNS regions. Myelin sheath length directly impacts axonal conduction velocity by influencing the spacing between nodes of Ranvier. Such differences likely affect neural signal coordination and synchronization. What accounts for regional differences in myelin sheath lengths is unknown; are myelin sheath lengths determined solely by axons or do intrinsic properties of different oligodendrocyte precursor cell populations affect length? The prevailing view is that axons provide molecular cues necessary for oligodendrocyte myelination and appropriate sheath lengths. This view is based upon the observation that axon diameters correlate with myelin sheath length, as well as reports that PNS axonal neuregulin-1 type III regulates the initiation and properties of Schwann cell myelin sheaths. However, in the CNS, no such instructive molecules have been shown to be required, and increasing in vitro evidence supports an oligodendrocyte-driven, neuron-independent ability to differentiate and form initial sheaths. We test this alternative signal-independent hypothesis—that variation in internode lengths reflects regional oligodendrocyte-intrinsic properties. Using microfibers, we find that oligodendrocytes have a remarkable ability to self-regulate the formation of compact, multilamellar myelin and generate sheaths of physiological length. Our results show that oligodendrocytes respond to fiber diameters and that spinal cord oligodendrocytes generate longer sheaths than cortical oligodendrocytes on fibers, co-cultures, and explants, revealing that oligodendrocytes have regional identity and generate different sheath lengths that mirror internodes in vivo. Oligodendrocytes, not Schwann cells, form myelin sheaths without axonal signals Oligodendrocytes sense diameter, increasing sheath length with larger fibers Oligodendrocytes from cortex and spinal cord form sheaths of different lengths Regional differences in sheath lengths may initially be hard-wired Much of the mammalian brain comprises axons wrapped by myelin sheaths, whose length determines conduction velocity. Bechler et al. overturn the long-held view that sheath-forming oligodendrocytes are all the same. Oligodendrocytes from different regions generate sheath lengths on microfibers and neurons that reflect their in vivo origin.