Transcriptional regulation of differentiation processes in myelinating glia of the mammalian CNS and PNS
In vertebrates, oligodendrocytes and Schwann cells, the myelinating glia of the central (CNS) and peripheral nervous system (PNS), ensheath large caliber axons to facilitate saltatory conduction. In humans, defects that compromise the generation of proper myelin or the integrity of already generated myelin sheaths result in different de- and dysmyelinating syndromes such as multiple sclerosis, Charcot-Marie-Tooth disease or a variety of leukodystrophies.
Understanding the mechanisms that regulate myelination and remyelination is an important step to develop new therapies for these diseases.
Generation of myelinating glia is a highly regulated process and requires the concerted action of transcriptional regulators and chromatin remodelling factors in a network that integrates intrinsic and extrinsic cues and leads to robust and accurately timed induction of myelination. Knowledge about single key transcriptional regulators is not sufficient to predict the complex regulation of oligodendrocyte and Schwann cell differentiation. Rather, interactions of many transcriptional regulators that reinforce or counteract each other`s function, together with drastic changes in chromatin architecture are necessary to ensure proper myelination. Additionally, those factors enable fast adaption of myelination to changes in the cellular environment during activity-dependent plastic myelination and remyelination of neuronal axons in the adult nervous system.
In my group we focus on the identification and functional analysis of novel regulators of glial differentiation as well as integration of these “new players” in the gene regulatory network. To accomplish this task we employ primary cell and organotypic tissue culture methods in addition to classical molecular biology methods, and analyze transgenic mouse models for further validation in vivo.