Transduction of Mechanical stimuli in myelination and peripheral nerve repair

机械生物学是一个新兴的领域，它研究物理力和变化如何影响细胞 分化、组织形成和疾病。这些力通过局部变化施加在细胞上。 在相邻细胞和细胞外基质之间。值得注意的是，细胞-细胞和细胞-细胞外基质 机械刺激可以刺激电化学反应，细胞骨架结构的重排和 基因表达的调节。 雪旺细胞是周围神经系统的髓鞘细胞，是发挥功能和 外周神经系统的健康状况。雪旺细胞在再生过程中也起着关键作用。 周围神经系统的潜能，但对雪旺细胞如何感知轴突损伤知之甚少。 我们证明了雪旺细胞对脑组织弹性的改变非常敏感。 细胞外基质；周围神经系统中雪旺细胞的分化和髓鞘形成 发育依赖于YAP和TAZ对机械刺激的转导。然而，目前还不清楚到底是什么 雪旺细胞中YAP和TAZ的上下游信令以及是否还需要YAP和TAZ 用于周围神经损伤后雪旺细胞的分化和再髓鞘形成。 在这里，我们将研究雪旺细胞中机械刺激的转导是否对刺激至关重要 髓鞘形成，促进周围神经再生。我们的目标是确定是否有可能 机械操作雪旺细胞以改善髓鞘形成，具有治疗意义(目标3)和 发现机械转导通路上游(Aim1)和下游(Aim2)的新组件 YAP和TAZ。通过机械转导分子YAP和TAZ研究髓鞘形成，有可能通过确定雪旺细胞和细胞机械生物学的治疗重要性来推动该领域的发展，并可能揭示新的 神经病分子中髓鞘形成和周围神经再生的靶点或机制。

Mechanobiology is an emerging field which studies how physical forces and changes can contribute to cell differentiation, tissue formation and diseases. These forces are applied on cells through the local variations between neighbouring cells and the extracellular matrix. Notably, cell—cell and cell-extracellular matrix mechanical stimuli can stimulate electrochemical responses, the rearrangement of cytoskeletal structures and the regulation of gene expression. Schwann cells, the myelinating cells of the peripheral nervous system, are required for the function and health of the peripheral nervous system. Schwann cells also have a critical role in the regenerative potential of the peripheral nervous system, but very little is known about how Schwann cells sense axonal injury. We demonstrated that Schwann cells are exquisitely sensitive to alterations in the elasticity of the extracellular matrix; and that Schwann cell differentiation and myelination during the peripheral nervous system development depend on the transduction of mechanical stimuli by YAP and TAZ. Yet, it is unknown what are the signalling upstream and downstream YAP and TAZ in Schwann cells and if YAP and TAZ are also required for Schwann cell differentiation and remyelination after peripheral nerve injury. Here we will investigate if the transduction of mechanical stimuli in Schwann cells is critical to stimulate myelination and improve peripheral nerve regeneration. Our objectives are to determine if it is possible to manipulate Schwann cells mechanically to improve myelination, with therapeutic implications (Aim 3) and to discover new components of the mechanotransduction pathways upstream (Aim1) and downstream (Aim 2) of YAP and TAZ. Studying myelination through the mechanotransducers YAP and TAZ has potential to advance the field by identifying the therapeutic importance of Schwann cell and cellular mechanobiology and may reveal novel targets or mechanisms for myelin formation and peripheral nerve regeneration in neuropathies molecular.