BREaking the Code of MYelin program

据推测，脊椎动物的出现可能是由于神经嵴细胞的获得，从而导致进化上有利的复杂头部结构的发展。在这方面，继神经嵴的获得之后，一个重要的衍生物——髓鞘——对脊椎动物成功的贡献必须指出。没有这种结构，我们所知道的脊椎动物就不可能存在。不幸的是，脱髓鞘在某些疾病中的发生，最常见的是多发性硬化症（MS），可能是有害的，并演变成永久性残疾。尽管自发性髓鞘再生是一种至关重要的修复机制，但有强有力的证据表明，尽管在病变内部或周围有大量的少突胶质细胞，但许多MS病变仍存在脱髓鞘。是什么阻止这些细胞形成髓鞘？是轴突缺乏必要的吸引信号，还是轴突在其表面表达了一些抑制分子？或者，少突胶质髓鞘形成程序是否受到某些因素的抑制？我们的目标是从一个完全创新的角度来解决这个问题。髓磷脂存在于绝大多数脊椎动物中。相反，在昆虫中，轴突通常只有一个胶质包裹，没有髓鞘。我们的工作假设是，打破触发果蝇鞘胶质细胞在轴突周围形成多个包裹的密码，将为修复MS病变打开大门，否则这些病变不会再髓鞘再生。我们的研究计划将解决诱导髓鞘形成程序的最低要求。我们项目的原创性和创新性依赖于实验模型的独特性（将无髓无脊椎动物和有髓脊椎动物相关联），这两个pi （B. Zalc和C. Klämbt）具有独特的能力和专业知识。

It has been postulated that the emergence of vertebrates was made possible by the acquisition of neural crest cells, which then led to the development of evolutionarily advantageous complex head structures. In this regard, consecutive to the acquisition of the neural crest, the contribution of one important derivative—the myelin sheath—to the success of the vertebrates has to be pointed out. Without this structure, the vertebrates, as we know them, simply could not exist. Unfortunately, occurrence of demyelination in some diseases, the most frequent being Multiple Sclerosis (MS), can be deleterious and evolve into permanent handicap. Even though spontaneous remyelination, a crucial repair mechanism, occurs in MS, there is strong evidence that many MS lesions remain demyelinated despite abundance of oligodendroglial cells within or around the lesions. What prevents these cells from myelinating? Are axons lacking a necessary attractive signal or are the axons expressing some inhibitory molecules at their surface? Alternatively, is the oligodendroglial myelination program inhibited by some factors? Our ambition is to tackle this problem from a completely innovative angle. Myelin is present in the vast majority of vertebrates. In contrast, in insects, axons generally have only a single glial wrap and are not myelinated. Our working hypothesis is that breaking the code that triggers Drosophila ensheathing glia to form multiple wraps around axons will open the door to cues to repair MS lesions that otherwise do not remyelinate. Our research proposal will address the minimal requirements to induce a myelination program. The originality and innovation of our project relies on the uniqueness of the experimental model (associating non-myelinated invertebrate and myelinated vertebrate), a combination for which the two PIs (B. Zalc and C. Klämbt) have the unique competence and expertise.