Developmental origin of oligodendrocytes determines their function in the adult brain

Foerster, Sarah; Floriddia, Elisa M; van Bruggen, David; Kukanja, Petra; Herve, Bastien; Cheng, Shangli; Kim, Eosu; Phillips, Benjamin U; Heath, Christopher J; Tripathi, Richa B; Call, Cody; Bartels, Theresa; Ridley, Katherine; Neumann, Bjorn; Lopez-Cruz, Laura; Crawford, Abbe H; Lynch, Cian J; Serrano, Manuel; Saksida, Lisa; Rowitch, David H; Möbius, Wiebke; Nave, Klaus-Armin; Rasband, Matthew N; Bergles, Dwight E; Kessaris, Nicoletta; Richardson, Willam D; Bussey, Timothy J; Zhao, Chao; Castelo-Branco, Goncalo and Franklin, Robin J M (2024). Developmental origin of oligodendrocytes determines their function in the adult brain. Nature Neuroscience, 27(8) pp. 1545–1554.

DOI: https://doi.org/10.1038/s41593-024-01666-8

Abstract

In the mouse embryonic forebrain, developmentally distinct oligodendrocyte progenitor cell (OPC) populations and their progeny, oligodendrocytes, emerge from three distinct regions in a spatiotemporal gradient from ventral to dorsal. However, the functional importance of this oligodendrocyte developmental heterogeneity is unknown. Using a genetic strategy to ablate dorsally-derived oligodendrocyte lineage cells (OLCs), here we show that the areas in which dorsally-derived OLCs normally reside in the adult CNS become populated and myelinated by OLCs of ventral origin. These ectopic oligodendrocytes (eOLs) have a distinctive gene expression profile, as well as subtle myelination abnormalities. The failure of eOLs to fully assume the role of the original dorsally-derived cells result in locomotor and cognitive deficits in the adult animal. This study reveals the importance of developmental heterogeneity within the oligodendrocyte lineage, and its importance for homeostatic brain function.