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

• Final Report Year: 2023

Final Report Abstract

This project, provocatively titled "Breaking the myelin code", has taken us much further than we had previously thought, but has also forced us to recognize the limitations of our system. Myelin is considered to be a typical glial specialization of the vertebrate nervous system to ensure rapid saltatory conduction. During the funding period, that was characterized by the Corona pandemic, we were first formulated a hypothesis suggesting the presence of myelinlike structures dependent on ephaptic effects and thus should occur also in invertebrates. In a next step we identified myelin-like structures in the adult Drosophila nervous system. A second aspect of the project was to identify the genes involved in the formation of myelin-like structures. We started to look at the importance of FGF and EGF signaling and also tested our initial hypothesis that neuronal activity plays a crucial role in glial differentiation. To do so, we specifically altered the activity of individual neurons. In order to characterize the effects of this manipulation at very high resolution, we have established the Apex2 technology in the Drosophila lab and are now able to manipulate individual neurons and simultaneously image them in the TEM. Unfortunately, all aTempts to activate or inactivate individual neurons have so far shown strong neurotoxic effects, making it impossible to investigate the contribution of neuronal activity to glial differentiation.

Publications

• Evolution of glial wrapping: A new hypothesis. Developmental Neurobiology, 81(5), 453-463.
  Rey, Simone; Zalc, Bernard & Klämbt, Christian
  
• Wrapping glia regulates neuronal signaling speed and precision in the peripheral nervous system of Drosophila. Nature Communications, 11(1).
  Kottmeier, Rita; Bittern, Jonas; Schoofs, Andreas; Scheiwe, Frederieke; Matzat, Till; Pankratz, Michael & Klämbt, Christian
  
• Axonal ion homeostasis and glial differentiation. The FEBS Journal, 290(15), 3737-3744.
  Rey, Simone; Ohm, Henrike & Klämbt, Christian
  
• Glial-dependent clustering of voltage-gated ion channels in Drosophila precedes myelin formation. eLife, 12.
  Rey, Simone; Ohm, Henrike; Moschref, Frederieke; Zeuschner, Dagmar; Praetz, Marit & Klämbt, Christian