Oligodendrocyte precursors guide inhibitory interneurons into the cerebral cortex via a novel molecular mechanism
A team from the University of Liège has just discovered a new function for oligodendrocyte precursors. These cells, which are responsible for the myelination of neurons in the adult nervous system, are also involved in guiding interneurons that settle in the cerebral cortex during embryonic development. Their results are published in the prestigious scientific journal Science.
The formation of the cerebral cortex requires the migration and settlement of some neural cells that are born in distant cerebral regions. This is the case for interneurons and some precursors of oligodendrocytes which are born in the ventral part of the developing brain. Once installed in the cortex, the interneurons tune cortical network activity and the oligodendrocytes produce the myelin which covers the axons of the neurons in order to facilitate the propagation of action potentials. Thus, the migration of these cells from their place of birth is important for their functional insertion within the cerebral cortex. However, cell migration could also contribute to the transmission of morphogenetic information to neighboring cells along the migration path. This hypothesis was tested by researchers from the molecular regulation of neurogenesis laboratory at GIGA (University of Liège), directed by Pr Laurent Nguyen (Research Director at FRS-FNRS). They have just discovered the existence of a molecular crosstalk between interneurons and oligodendrocyte precursors during their migration, which is responsible for the unidirectional repulsion of interneurons via the semaphorin/plexin molecular system. This new mode of cell repulsion contribute to the guidance of interneurons in the cortex by preventing them from aggregating around blood vessels. The researchers' results also suggest that a dysfunction in this molecular dialogue between oligodendrocyte precursors and interneurons could underlie the emergence of neurodevelopmental diseases such as autism and epilepsy. This work demonstrates the existence of a new non-canonical function of oligodendrocyte precursors (independent of axon myelination) which is important for the construction of the cerebral cortex. New perspectives open up following these results. “This finding likely represents only the tip of the iceberg since there are many cell populations migrating simultaneously in the developing cortex. It therefore paves the way for a better understanding of the molecular dialogues that are established between these moving cells and their environment to shape the cerebral cortex,” explains Laurent Nguyen. The analysis of these cellular interactions is in progress and is the topic of a new research project funded by Welbio.
Time-lapse sequence showing unidirectional repulsion (UCoRe) of a cortical interneuron (red) by an oligodendrocyte precursor (green).
Cortical interneurons (cIN, red) and some oligodendrocyte precursors (vOPC, green) originate in ventral regions of the developing brain (MGE, medial ganglionic eminence; POA, preoptic area) and migrate to the cerebral cortex. vOPCs induce unidirectional repulsion (UCoRe which depends on the interaction between semaphorins 6a/6b, expressed by vOPCs and plexin A3, expressed by cINs) of cINs, a process that participates in the guidance of cINs in the cortex by preventing their aggregation around theblood vessels (which releases the chemokine Cxcl12 which attracts vOPCs and cINs).
Reference
Oligodendrocyte precursors guide interneuron migration by unidirectional contact repulsion
Fanny Lepiemme, Julie Stoufflet, Miriam Javier-Torrent, Gabriel Mazzucchelli, Carla G. Silva, Laurent Nguyen.
Science 376, eabn6204 (2022). DOI: 10.1126/science.abn6204
