BREaking the Code of MYelin program

• Applicant: Professor Dr. Christian Klämbt
• Subject Area: Developmental Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 406563665

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.

• DFG Programme: Research Grants
• International Connection: France
• Partner Organisation: Agence Nationale de la Recherche / The French National Research Agency
• Cooperation Partner: Professor Dr. Bernard Zalc