Tricaud Nicolas
Institut National de la Santé et de la Recherche Médicale, Institut des Neurosciences de Montpellier, Université de Montpellier, Montpellier, France.
Front Cell Neurosci. 2018 Jan 5;11:414. doi: 10.3389/fncel.2017.00414. eCollection 2017.
Myelin sheath geometry, encompassing myelin sheath thickness relative to internodal length, is critical to optimize nerve conduction velocity and these parameters are carefully adjusted by the myelinating cells in mammals. In the central nervous system these adjustments could regulate neuronal activities while in the peripheral nervous system they lead to the optimization and the reliability of the nerve conduction velocity. However, the physiological and cellular mechanisms that underlie myelin sheath geometry regulation are not yet fully elucidated. In peripheral nerves the myelinating Schwann cell uses several molecular mechanisms to reach and maintain the correct myelin sheath geometry, such that myelin sheath thickness and internodal length are regulated independently. One of these mechanisms is the epithelial-like cell polarization process that occurs during the early phases of the myelin biogenesis. Epithelial cell polarization factors are known to control cell size and morphology in invertebrates and mammals making these processes critical in the organogenesis. Correlative data indicate that internodal length is regulated by postnatal body growth that elongates peripheral nerves in mammals. In addition, the mechanical stretching of peripheral nerves in adult animals shows that myelin sheath length can be increased by mechanical cues. Recent results describe the important role of YAP/TAZ co-transcription factors during Schwann cell myelination and their functions have linked to the mechanotransduction through the HIPPO pathway and the epithelial polarity factor Crb3. In this review the molecular mechanisms that govern mechanically-driven myelin sheath elongation and how a Schwann cell can modulate internodal myelin sheath length, independent of internodal thickness, will be discussed regarding these recent data. In addition, the potential relevance of these mechanosensitive mechanisms in peripheral pathologies will be highlighted.
髓鞘几何结构，包括髓鞘厚度与结间长度的关系，对于优化神经传导速度至关重要，并且这些参数在哺乳动物中由髓鞘形成细胞进行精确调节。在中枢神经系统中，这些调节可调控神经元活动，而在周围神经系统中，它们可使神经传导速度得到优化并提高可靠性。然而，髓鞘几何结构调节背后的生理和细胞机制尚未完全阐明。在周围神经中，形成髓鞘的施万细胞利用多种分子机制来达到并维持正确的髓鞘几何结构，从而使髓鞘厚度和结间长度能够独立调节。其中一种机制是在髓鞘生物发生早期阶段发生的上皮样细胞极化过程。已知上皮细胞极化因子可控制无脊椎动物和哺乳动物中的细胞大小和形态，使得这些过程在器官发生中至关重要。相关数据表明，结间长度受出生后身体生长的调节，这种生长会使哺乳动物的周围神经伸长。此外，成年动物周围神经的机械拉伸表明，髓鞘长度可通过机械信号增加。最近的研究结果描述了YAP/TAZ共转录因子在施万细胞髓鞘形成过程中的重要作用，并且它们的功能与通过HIPPO途径的机械转导以及上皮极性因子Crb3相关。在本综述中，将结合这些最新数据讨论控制机械驱动的髓鞘伸长的分子机制，以及施万细胞如何独立于结间厚度调节结间髓鞘长度。此外，还将强调这些机械敏感机制在周围病理学中的潜在相关性。
