Developmental origin of oligodendrocytes determines their function in the adult brain

作者：Sarah Foerster, Elisa M. Floriddia, David van Bruggen, Petra Kukanja, Bastien Hervé, Shangli Cheng, Eosu Kim, Benjamin U. Phillips, Christopher J. Heath, Richa B. Tripathi, Cody L. Call, Theresa Bartels, Katherine Ridley, Björn Neumann, Laura López‐Cruz, Abbe Harper Crawford, Cian J. Lynch, Manuel Serrano, Lisa M. Saksida, David H. Rowitch, Wiebke Möbius, Klaus‐Armin Nave, Matthew Neil Rasband, Dwight E. Bergles, Nicoletta Kessaris, William David Richardson, Timothy J. Bussey, Chao Zhao, Gonçalo Castelo‐Branco, Robin J.M. Franklin · 发表于：Nature Neuroscience · 年份：2024 · DOI：10.1038/s41593-024-01666-8 · 被引用次数：48 · 研究领域：Neurogenesis and neuroplasticity mechanisms、Neuroinflammation and Neurodegeneration Mechanisms、Single-cell and spatial transcriptomics

In the mouse embryonic forebrain, developmentally distinct oligodendrocyte progenitor cell 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), we show here that the areas in which dorsally derived OLCs normally reside in the adult central nervous system 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 results 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.