Are there different mechanisms of oligodendrocyte recruitment when new myelin is made during nervous system plasticity and regeneration?

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Our central nervous system (CNS), which comprises brain and spinal cord, consists of myriads of cells that constantly interact and influence each other. Nerve cells (neurons) are the main information processing unit in the CNS, which form a network that is interconnected via long cell processes called axons.Neurons and their axons are not alone in the brain, but their function critically depends on the presence of surrounding support cells, for which the umbrella term 'glial cells' is used. One specific type of such glial cells are oligodendrocytes. Oligodendrocytes form an insulating substance around axons which is called myelin, and which is in fact the 'white' in the white matter of our brain.Myelin formation by oligodendrocytes is absolutely crucial for nervous system function. It insulates and feeds axons, and in doing so enables rapid information processing between neurons.New myelin can dynamically be formed in the healthy CNS almost lifelong and is of importance for structural changes within our CNS that underlie learning. Damage of myelin has devastating neurological consequences and is a hallmark of demyelinating diseases such as Multiple Sclerosis (MS). Damaged myelin can get repaired in an endogenous regenerative process called remyelination. Both, myelination in the healthy CNS and remyelination in the diseased CNS are carried out by oligodendrocytes. For a long time, oligodendrocytes have been considered a homogenous cell population. However, recent research results revealed that oligodendrocytes are diverse and have different properties and functions.Therefore, it is an important open question if new myelin formed in the healthy and diseased CNS is made by the same or by different oligodendrocytes and how this is controlled. It is important to gain knowledge of the regulatory principles that underlie these processes in order device strategies of how to specifically target oligodendrocytes when these processes naturally fail to occur.In this proposal, we use a unique approach with which to address the question of how new myelin is made in the healthy and in the damaged CNS. We will use small tropical zebrafish as model organisms because young zebrafish are optically transparent, allowing us to investigate all oligodendrocytes in the CNS of a living animal in real time without the need of any surgical intervention. Being able to easily see how different oligodendrocytes master myelin formation in the healthy CNS, as well as remyelination in the damaged CNS, will allow us to unambiguously answer whether oligodendrocytes with similar or different properties are involved. Furthermore, because we will also analyse genetic information of the oligodendrocytes that we investigate, we will gain knowledge on how this is controlled by our genes. Together, our work will lead to the discovery of potentially new pathways which govern myelin formation in the healthy and damaged brain; and may therefore permit the development of new strategies to specifically manipulate these processes where they fail to occur naturally.