Oligodendrocyte precursor cells guide the migration of cortical interneurons by unidirectional contact repulsion

Abstract

The cerebral cortex is built by neural cells that migrate away from their birthplace. In the forebrain, ventrally-derived oligodendrocyte precursor cells (vOPCs) travel tangentially together with cortical interneurons (cINs) to reach the cortex. After birth, vOPCs form transient synapses with cINs before engaging later into myelination. Here we tested whether these populations interact during embryogenesis while migrating. By coupling histological analysis of mouse genetic models with live imaging, we showed that, while responding to the chemokine Cxcl12, vOPCs and cINs occupy mutually-exclusive forebrain territories. Moreover, vOPCs depletion selectively disrupts the migration and distribution of cINs. At the cellular level, we found that by promoting unidirectional contact-repulsion (UCoRe) of cINs, vOPCs steer their migration away from blood vessels and contribute to their allocation to proper migratory streams. UCoRe is thus an efficient strategy to spatially control the competition for a shared chemoattractant, thereby allowing cINs to reach proper cortical territories.

Novel in vitro Experimental Approaches to Study Myelination and Remyelination in the Central Nervous System

“…When assembling ventral and dorsal organoids, dorsally derived oligodendroglial cells outcompete ventrally derived oligodendroglia and become dominant after long-term culture ( Kim et al, 2019 ). These results are in line with recent observations about the specific impact of ventral OPCs on the migration and maturation of mouse cortical interneurons ( Lepiemme et al, 2021 ). These pioneering studies demonstrated that generating brain organoids with myelinating OLs is indeed possible, however, they require very long protocols (from 110 to 210 days) to produce myelinated fibers.…”