Developmental origin of oligodendrocytes determines their function in the adult brain

少突胶质细胞的发育起源决定了它们在成年大脑中的功能

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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 Call ,Theresa Bartels ,Katherine Ridley ,Björn Neumann ,Laura López-Cruz ,Abbe H Crawford ,Cian J Lynch ,Manuel Serrano ,Lisa Saksida ,David H Rowitch ,Wiebke Möbius ,Klaus-Armin Nave ,Matthew N Rasband ,Dwight E Bergles ,Nicoletta Kessaris ,William D Richardson ,Timothy J Bussey ,Chao Zhao ,Gonçalo Castelo-Branco ,Robin J M Franklin

Abstract

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.

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