UCL Discovery

Abstract

During development oligodendrocyte progenitor cells (OLPs) are responsible for the production of oligodendrocytes. Cells with similar antigenic properties to developmental OLPs persist throughout postnatal life, beyond the cessation of “developmental” myelination. These postnatal cells are often referred to as “NG2 cells” because they (and their perinatal counterparts) express the NG2 proteoglycan, but little is known about their function in the adult brain. Experiments documented in this Thesis use transgenic lineage tracing technology to characterize the in vivo behavior of OLPs in the brain at various ages. Fate mapping of OLPs revealed that they give rise to oligodendrocytes throughout life. In addition, OLPs were shown to generate a small proportion of the projection neurons present in the posterior piriform cortex, while no evidence for astrogliogenesis from OLPs was found. Cumulative in vivo labelling of OLPs with thymidine analogues (BrdU and EdU) showed that they proliferate continuously throughout life with an increasing cell cycle time with age. At all ages examined, there was a proportion of OLPs that never underwent cell division, indicating that there are cycling and non-cycling populations of OLPs in the mouse brain that persist throughout life. The observed contribution of adult-born oligodendrocytes to myelinating the brain was surprisingly large, and raised intriguing questions as to the necessity and function of these new myelinating cells. To investigate this directly, I generated a new transgenic mouse line that when crossed to a transgenic mouse that expresses an inducible form of Cre, can be used to selectively ablate the myelinating oligodendrocytes produced in adult life.

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