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Venkataramanappa, Sathish; Saaber, Friederike; Abe, Philipp; Schütz, Dagmar; Kumar, Praveen Ashok; Stumm, Ralf
Cell reports (Cambridge), 08/2022, Letnik: 40, Številka: 5Journal Article
The function of the cerebral cortex depends on various types of interneurons (cortical interneurons cINs) and their appropriate allocation to the cortical layers. Caudal ganglionic eminence-derived cINs (cGE-cINs) are enriched in superficial layers. Developmental mechanisms directing cGE-cINs toward superficial layers remain poorly understood. We examine how developmental and final positioning of cGE-cINs are influenced by the Cxcl12, Cxcr4, Ackr3 module, the chief attractant system guiding medial ganglionic eminence-derived cINs (mGE-cINs). We find that Cxcl12 attracts cGE-cINs through Cxcr4 and supports their layer-specific positioning in the developing cortex. This requires the prevention of excessive Cxcr4 stimulation by Ackr3-mediated Cxcl12 sequestration. Postnatally, Ackr3 confines Cxcl12 action to the marginal zone. Unlike mGE-cINs, cGE-cINs continue to express Cxcr4 at early postnatal stages, which permits cGE-cINs to become positioned in the forming layer 1. Thus, chemoattraction by Cxcl12 guides cGE-cINs and holds them in superficial cortical layers. Display omitted •Layer 1 interneurons express Cxcr4 during the perinatal period•Interneuron allocation to layer 1 requires Cxcl12-Cxcr4 signaling in the marginal zone•Ackr3 modulates Cxcl12-dependent interneuron positioning in the marginal zone•Timing of Cxcr4 expression contributes to the different layering of cIN subtypes Venkataramanappa et al. investigate how the layering characteristics of different cerebro-cortical interneuron types arise. They identify a neonatal Ackr3-dependent submeningeal Cxcl12 niche holding interneurons in superficial layers via Cxcr4 signaling. They conclude that timing of Cxcr4 expression and Ackr3-regulated Cxcl12 availability contribute to upper layer allocation of distinct interneuron types.
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