Oligodendrocyte precursors guide interneuron migration by unidirectional contact repulsion

Abstract

In the forebrain, ventrally derived oligodendrocyte precursor cells (vOPCs) travel tangentially toward the cortex together with cortical interneurons. Here, we tested in the mouse whether these populations interact during embryogenesis while migrating. By coupling histological analysis of genetic models with live imaging, we show that although they are both attracted by the chemokine Cxcl12, vOPCs and cortical interneurons occupy mutually exclusive forebrain territories enriched in this chemokine. Moreover, first-wave vOPC depletion selectively disrupts the migration and distribution of cortical interneurons. At the cellular level, we found that by promoting unidirectional contact repulsion, first-wave vOPCs steered the migration of cortical interneurons away from the blood vessels to which they were both attracted, thereby allowing interneurons to reach their proper cortical territories.

Neuron‐glia crosstalk shapes brain morphogenesis

“… 1 This is exemplified by recent works showing that cell migration conveys key instructive cues to neighbouring cells in the developing cortex. 2 , 3 , 4 , 5 Cortical neurons, which comprise interneurons (cINs) born in the subpallium and projection neurons (PNs) generated in the pallium, undergo migration to settle in ad hoc cortical layers where they functionally integrate circuits. The cINs migrate along tangential paths to reach the cortex, a process during which they engage in cellular crosstalk and read extracellular cues to find their way.…”

“…Along this line, our laboratory discovered that some oligodendrocyte precursor cells (OPCs) steer the migration of cINs in the forebrain via direct contact. 4 Cerebral OPCs are generated in three competitive waves: two initial ones, born during embryogenesis in the ganglionic eminences and the preoptic area, and a third one that arises from cortical progenitors around birth. 9 Third‐wave OPCs generate most oligodendrocytes that myelinate later PN axons while some 1st wave ventrally‐derived OPCs (vOPCs) form GABAergic synapses with lineage‐related cINs 10 and later contribute to cIN myelination.…”

“…While cINs navigate within the cortex in organized streams, 1st wave vOPCs undergo random walking and later disperse via dynamic gliding along the blood vessels (BVs) that are growing in the forebrain. 4 , 12 The conditional elimination of vOPCs results in a less cortical invasion by cINs. Both vOPCs and cINs are attracted by Cxcl12 locally released by BVs, but 1st wave vOPCs are the ones covering BVs because they prevent cINs to interact with BVs via unidirectional contact repulsion (UCoRe).…”

“…Cell migration not only brings precursors to their final position in the cortex but also promotes transient interactions with other cells, thereby conferring additional roles to those played once integrated into the cortical network 1 . This is exemplified by recent works showing that cell migration conveys key instructive cues to neighbouring cells in the developing cortex 2–5 . Cortical neurons, which comprise interneurons (cINs) born in the subpallium and projection neurons (PNs) generated in the pallium, undergo migration to settle in ad hoc cortical layers where they functionally integrate circuits.…”

“…Therefore, loss of 1st wave vOPCs leads to the accumulation of cINs in the vicinity of BVs, where they tend to aggregate. UCoRe is a repulsive signalling mediated by the interaction between PlexinA3 (expressed by cINs) and Sema6a/b (by 1st wave vOPCs), which causes cINs to retract their leading process, change polarity and migrate away from the 1st wave vOPCs 4 . This cell behaviour can be compared to a tennis ball (cIN) bouncing back on the opponent's racket (1st wave vOPC) during a volley shot.…”