{
  "abstract": "The human brain is distinguished by unusually prolonged developmental timing, yet the genetic mechanisms coordinating this neoteny across cell types remain incompletely understood. Here, we show that human cortical microglia undergo neotenic structural and transcriptional maturation relative to mouse microglia. We identify SRGAP2B/C, human-specific paralogs of the ancestral SRGAP2A, as the only human-specific gene duplications expressed in human microglia. Using xenotransplantation of human induced pluripotent stem cell (hiPSC)-derived microglia and mouse genetic models, we demonstrate that human-specific SRGAP2B/C, previously shown to reduce SRGAP2A protein abundance, are both necessary and sufficient to induce neotenic structural microglial maturation. Our results reveal that neotenic microglial maturation modifies the timing of synaptic development, linking microglial developmental programs to the timing of circuit formation. Together with previous evidence for neuronal SRGAP2A function, our results suggest that the human-specific SRGAP2B/C paralogs coordinated the emergence of neotenic synaptic development by acting in both neurons and microglia during human brain evolution.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neuroscience, Columbia University, New York, NY 10027, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA. Electronic address: carldiaz1992@gmail.com",
    "Weill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA",
    "School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK",
    "Department of Neuroscience, Columbia University, New York, NY 10027, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA",
    "Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA",
    "Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA",
    "Department of Neuroscience, Columbia University, New York, NY 10027, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA. Electronic address: fp2304@columbia.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Carlos Diaz-Salazar"
    },
    {
      "affs": [
        1
      ],
      "name": "JaeYeon Kim"
    },
    {
      "affs": [
        2
      ],
      "name": "Marine Krzisch",
      "orcid": "0000-0002-9964-7992"
    },
    {
      "affs": [
        3
      ],
      "name": "Juyoun Yoo",
      "orcid": "0000-0002-4600-7094"
    },
    {
      "affs": [
        4
      ],
      "name": "Patricia R. Nano",
      "orcid": "0000-0002-5507-2656"
    },
    {
      "affs": [
        4
      ],
      "name": "Aparna Bhaduri",
      "orcid": "0000-0003-4625-6899"
    },
    {
      "affs": [
        5
      ],
      "name": "Rudolf Jaenisch",
      "orcid": "0000-0002-2540-7099"
    },
    {
      "affs": [
        1
      ],
      "name": "Mercedes Paredes"
    },
    {
      "affs": [
        6
      ],
      "name": "Franck Polleux",
      "orcid": "0000-0003-4313-0481"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cq7tkjvyfxh7e.bib",
  "cited_by": 5,
  "doi": "10.1016/j.neuron.2026.07.007",
  "fulltext_url": null,
  "id": "cq7tkjvyfxh7e",
  "issns": [
    "0896-6273",
    "1097-4199"
  ],
  "landing_url": "https://doi.org/10.1016/j.neuron.2026.07.007",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7171562763",
  "pdf_url": null,
  "pmcid": "PMC13426080",
  "pmid": "42520792",
  "published": "2026-07-28",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/cq7tkjvyfxh7e.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T13:20:49Z",
      "native_id": "W7171562763",
      "source": "openalex",
      "url": "https://doi.org/10.1016/j.neuron.2026.07.007"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Human-specific SRGAP2 paralogs synchronize neotenic microglial maturation and synaptic development",
  "title_text": "Human-specific SRGAP2 paralogs synchronize neotenic microglial maturation and synaptic development",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:14Z",
  "url": "https://research.draconitic.com/paper/cq7tkjvyfxh7e",
  "venue": "Neuron",
  "versions": []
}