Periodic Reporting for period 4 - MecMy (Mechanisms of Myelination – Elucidating the Diversity of Oligodendroglial Precursors and their Local Axon-Glia Interactions)
Período documentado: 2021-08-01 hasta 2022-08-31
Most connections between nerve cells (axons) are eventually surrounded with myelin, an insulating structure produced by specialized glia called oligodendrocytes. This cellular interaction enables fast signal transmission, ensures long-term axon survival, and is involved in regulating learning and memory formation.
The formation of new myelin during lifelong development and after myelin damage requires differentiation of oligodendrocyte precursors. Although these cells are an abundant population in our brains lifelong, myelin repair is often inefficient and eventually fails. It is known that oligodendroglial precursors have diverse properties, but whether this diversity is at any level a regulatory factor for normal myelination, or causal to failure of myelin repair is unclear.
In this action, we elucidate the diversity of oligodendrocyte precursors by carrying out a clonal analysis of oligodendrocyte properties and fates in order to address if all oligodendrocyte are equally capable to contribute to myelin formation, and to investigate how these cells might differ.
To achieve these goals we use zebrafish, an ideally suited model organism for in vivo live cell imaging and genetic manipulation. We carry out a clonal analysis of oligodendrocyte precursor population dynamics during myelinated tract formation. We analyse the molecular signature of cells with different properties, profile their physiology and their cell fate responses to external manipulation.
This work will provide fundamentally new insights into the principles of the heterogeneity of oligodendroglial precursors and may help to device new strategies of how to employ these cells to form new myelin in development and disease.