Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution

Microglia, essential in the central nervous system (CNS), were historically considered absent from the peripheral nervous system (PNS). Here, we show a PNS-resident macrophage population that shares transcriptomic and epigenetic profiles as well as an ontogenetic trajectory with CNS microglia. This population (termed PNS microglia-like cells) enwraps the neuronal soma inside the satellite glial cell envelope, preferentially associates with larger neurons during PNS development, and is required for neuronal functions by regulating soma enlargement and axon growth. A phylogenetic survey of 24 vertebrates revealed an early origin of PNS microglia-like cells, whose presence is correlated with neuronal soma size (and body size) rather than evolutionary distance. Consistent with their requirement for soma enlargement, PNS microglia-like cells are maintained in vertebrates with large peripheral neuronal soma but absent when neurons evolve to have smaller soma. Our study thus reveals a PNS counterpart of CNS microglia that regulates neuronal soma size during both evolution and ontogeny.