Microglial control of neuronal development via somatic purinergic junctions

• Published in: Cell reports (Cambridge) Vol. 40; no. 12; p. 111369
• Main Authors: Cserép, Csaba, Schwarcz, Anett D., Pósfai, Balázs, László, Zsófia I., Kellermayer, Anna, Környei, Zsuzsanna, Kisfali, Máté, Nyerges, Miklós, Lele, Zsolt, Katona, István, Ádám Dénes
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.09.2022
• Subjects: Adult; Brain; doublecortin; Humans; microglia; Microglia - physiology; Neurogenesis; neuronal development; Neurons - physiology; P2Y12R; purinergic; somatic junction; neuronal development; doublecortin; purinergic; somatic junction; CP: Neuroscience; P2Y12R; microglia
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111369

Microglia, the resident immune cells of the brain, play important roles during development. Although bi-directional communication between microglia and neuronal progenitors or immature neurons has been demonstrated, the main sites of interaction and the underlying mechanisms remain elusive. By using advanced methods, here we provide evidence that microglial processes form specialized contacts with the cell bodies of developing neurons throughout embryonic, early postnatal, and adult neurogenesis. These early developmental contacts are highly reminiscent of somatic purinergic junctions that are instrumental for microglia-neuron communication in the adult brain. The formation and maintenance of these junctions is regulated by functional microglial P2Y12 receptors, and deletion of P2Y12Rs disturbs proliferation of neuronal precursors and leads to aberrant cortical cytoarchitecture during development and in adulthood. We propose that early developmental formation of somatic purinergic junctions represents an important interface for microglia to monitor the status of immature neurons and control neurodevelopment. [Display omitted] •Microglial processes contact specialized areas of developing neuronal cell bodies•Somatic junctions possess specialized molecular patterns and ultrastructure•Somatic junctions are dynamic and require P2Y12R signaling to shape neurodevelopment•Lack of microglial P2Y12Rs leads to erratic cortical cytoarchitecture in adulthood Cserép et al. show that microglial processes contact specialized areas of immature postmitotic neurons during neurogenesis. Somatic purinergic junctions possess unique nano-architecture and are highly dynamic and P2Y12R-dependent. These intercellular interactions enable microglia to monitor and shape neurodevelopment and promote neuronal integration within cortical networks.