Evidence map›Paper›PMID 42520792›Full record

ArticleNeuron2026

Human-specific SRGAP2 paralogs synchronize neotenic microglial maturation and synaptic development.

Carlos Diaz-Salazar, JaeYeon Kim, Marine Krzisch, Juyoun Yoo, Patricia R Nano, Aparna Bhaduri, Rudolf Jaenisch, Mercedes Paredes, Franck Polleux

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Zebrafish models of human-duplicatedbioRxiv : the preprint server for biology · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Carlos Diaz-SalazarDepartment 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.
JaeYeon KimWeill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.
Marine KrzischSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Juyoun YooDepartment of Neuroscience, Columbia University, New York, NY 10027, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Patricia R NanoWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Aparna BhaduriWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Rudolf JaenischDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Mercedes ParedesWeill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.
Franck PolleuxDepartment 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.

Funding

Development, Maintenance, and Human-Specific Evolution of Cortical CircuitsR35NS127232 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FRANCK POLLEUX · 2022 to 2026
$6.1M
Elucidating Regulation of Cell Fate Specification in Human Cortical Development to Understand Etiology of Neurodevelopment DisordersR01MH132689 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Aparna Bhaduri · 2024 to 2026
$2.1M
Protracted Maturation of Cortical Inhibitory Neurons for the Complexity of Higher Cognitive AreasK99NS138587 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jaeyeon Kim · 2025 to 2026
$231k
NIMH NIH HHS R01 MH132689NINDS NIH HHS K99 NS138587NINDS NIH HHS R35 NS127232
6 · The paper itself

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.

Indexed as

GTPase-Activating ProteinsMicrogliaSynapsesAnimalsBrainHumansInduced Pluripotent Stem CellsMiceNeurodevelopmentNeuronsGTPase-Activating ProteinsSRGAP2 protein, humanbrainevolutionhumanhuman-specific gene duplicationmicrogliamouseneotenyneuronssynapsesxenotransplantation

Identifiers

PMID42520792
PMCPMC13426080

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.