Iannarelli, P; (2017) Oligodendrocyte Population Dynamics and Plasticity Probed by Genetic Manipulation in Mice. Doctoral thesis , UCL (University College London).

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Abstract

During embryonic development, oliogdendrocyte precursor cells (OLPs) originate in the ventral region of the neural tube, and from this area proliferate and migrate throughout the entire CNS. Work from several labs has shown dorsal regions of the neural tube can also be an additional source of OLPs. Ventrally and dorsallyderived OLPs are thought to be specified differently, since morphogenic signals that are known to specify ventral OLPs are absent in the dorsal regions of the CNS. However, the question remains whether oligodendrocyte (OLs) with different developmental origins are functionally equivalent or not. If there are different specialized subtypes of OLPs and OLs, this might need to be taken into consideration when designing therapies for demyelinating diseases based on transplantation of pure OLPs from various sources. To address the question, I specifically ablated particular OL lineage cells with different developmental origins using a Cre/loxP system and Diphtheria toxin A chain (DTA). A transgenic mouse line was generated that carried DTA under the transcriptional control of Sox10, which is expressed in all OLPs regardless of their developmental origin. Upstream of the DTA open reading frame were sequences encoding the enhanced green fluorescent protein (EGFP) allowing expression of the toxin only after the floxed EGFP was excised. In order to selectively eliminate OLPs from ventral or dorsal origin, the Sox10-DTA mouse line was crossed with a line that expresses Cre recombinase selectively in dorsal or ventral regions of the developing telencephalon. I found that when either dorsal or ventral-derived OLPs were ablated with DTA, neighbouring OLP populations moved in to replace the missing cells. When ventrally-derived OLPs were ablated there was a slight delay in the accumulation of OLPs and in the onset of myelination. Even when all telencephalic-derived OLPs, both ventral and dorsal, were ablated, populations from more posterior brain regions made up for the loss. This work strongly suggests that OLPs, in the developing telencephalon, from dorsal and ventral origins are functionally equivalent.

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