Laouarem Yousra, Traiffort Elisabeth
Small Molecules of Neuroprotection, Neuroregeneration and Remyelination - U1195, INSERM, University Paris-Sud/Paris-Saclay, Kremlin-Bicêtre, France.
Front Cell Neurosci. 2018 Sep 6;12:305. doi: 10.3389/fncel.2018.00305. eCollection 2018.
Since the discovery of its role as a morphogen directing ventral patterning of the spinal cord, the secreted protein Sonic Hedgehog (Shh) has been implicated in a wide array of events contributing to the development, maintenance and repair of the central nervous system (CNS). One of these events is the generation of oligodendrocytes, the glial cells of the CNS responsible for axon myelination. In embryo, the first oligodendroglial cells arise from the ventral ventricular zone in the developing brain and spinal cord where Shh induces the basic helix-loop-helix transcription factors Olig1 and Olig2 both necessary and sufficient for oligodendrocyte production. Later on, Shh signaling participates in the production of oligodendroglial cells in the dorsal ventricular-subventricular zone in the postnatal forebrain. Finally, the modulation of Hedgehog signaling activity promotes the repair of demyelinated lesions. This mini-review article focuses on the Shh-dependent molecular mechanisms involved in the spatial and temporal control of oligodendrocyte lineage appearance. The apparent intricacy of the roles of two essential components of Shh signaling, Smoothened and Gli1, in the postnatal production of myelin and its regeneration following a demyelinating event is also highlighted. A deeper understanding of the implication of each of the components that regulate oligodendrogenesis and myelination should beneficially influence the therapeutic strategies in the field of myelin diseases.
自从发现分泌蛋白音猬因子（Shh）作为一种形态发生素指导脊髓腹侧模式形成以来，它已被证明参与了一系列有助于中枢神经系统（CNS）发育、维持和修复的事件。其中一个事件是少突胶质细胞的产生，少突胶质细胞是中枢神经系统中负责轴突髓鞘形成的神经胶质细胞。在胚胎中，第一批少突胶质细胞起源于发育中的脑和脊髓的腹侧脑室区，在那里Shh诱导碱性螺旋-环-螺旋转录因子Olig1和Olig2，这两个因子对于少突胶质细胞的产生既是必需的也是充分的。后来，Shh信号通路参与了出生后前脑背侧脑室-室下区少突胶质细胞的产生。最后，刺猬信号通路活性的调节促进了脱髓鞘病变的修复。这篇综述文章重点关注了参与少突胶质细胞谱系出现的时空控制的Shh依赖性分子机制。还强调了Shh信号通路的两个重要组成部分，即平滑肌瘤蛋白（Smoothened）和Gli1，在出生后髓鞘生成及其在脱髓鞘事件后的再生中的作用的明显复杂性。对调节少突胶质细胞生成和髓鞘形成的每个成分的影响有更深入的了解，应该会对髓鞘疾病领域的治疗策略产生有益的影响。
