The Dorsoventral Boundary of the Germinal Zone is a Specialized Niche for the Generation of Cortical Oligodendrocytes during a Restricted Temporal Window

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Abstract

Oligodendrocyte precursor cells (OPCs) appear in the late embryonic brain, mature to become oligodendrocytes (OLs), and form myelin in the postnatal brain. Recently, it has been proposed that early-born OPCs derived from the ventral forebrain are eradicated postnatally and that late-born OLs predominate in the cortex of the adult mouse brain. However, intrinsic and extrinsic factors that specify the ability of self-renewing multipotent neural stem cells in the embryonic brain to generate cortical OL-lineage cells remain largely unknown. Using an inducible Cre/loxP system to permanently label Nestin- and Olig2-lineage cells, we identified that cortical OL-lineage cells start differentiating from neural stem cells within a restricted temporal window just prior to E16.5 through P10. We then showed, by means of electroporation of a Cre expression plasmid into the VZ/SVZ of E15.5 reporter mouse brains, that neural precursor cells in the dorsal VZ/SVZ are inhibited by Wnt signaling from contributing to cortical OLs in the adult brain. In contrast, neural precursor cells present in the dorsoventral boundary VZ/SVZ produce a significant amount of OLs in the adult cortex. Our results suggest that neural stem cells at this boundary are uniquely specialized to produce myelin-forming OLs in the cortex.

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