PreprintCited by 82Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeurogenesis and neuroplasticity mechanisms

A cross-species proteomic map reveals neoteny of human synapse development

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Wang, Li, Pang, Kaifang, Zhou, Li, Cebrián-Silla, Arantxa, González-Granero, Susana, Wang, Shaohui, Bi, Qiuli, White, Matthew L. +17 more·2022·Nature

Preprint — published as 10.1038/s41586-023-06542-2 · Paper page

Abstract

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood. Here, we generated a cross-species proteomic map of synapse development in the human, macaque, and mouse neocortex. By tracking the changes of >1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we found that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that the human PSD matures about two to three times slower than other species and contains higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of the RhoGEF signaling in human neurons delays the morphological maturation of dendritic spines and the functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Together, our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation.

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Authors
Wang, L., Pang, K., Zhou, L., Cebrián-Silla, A., González-Granero, S., Wang, S., Bi, Q., White, M. L., Ho, B., Li, J., Li, T., Perez, Y., Huang, E. J., Winkler, E. A., Paredes, M. F., Kovner, R., Sestan, N., Pollen, A. A., Liu, P., Li, J., Piao, X., García-Verdugo, J. M., Alvarez-Buylla, A., Liu, Z., & Kriegstein, A. R.
Affiliations
  • University of California, San Francisco (US)
  • Baylor College of Medicine (US)
  • Universitat de València (ES)
  • Yale University (US)
  • University of Massachusetts Lowell (US)
Corresponding author
  • Wang, Li
  • Kriegstein, Arnold R.
Venue
Nature
Publisher
openRxiv
Published
2022-10-25
Volume
622
Issue
7981
Pages
112-119
ISSN
0028-0836 (ISSN-L)
OpenAlex
W4386697742
Cited by
82
References
112
Citations by year
2026: 22 · 2025: 28 · 2024: 24 · 2023: 8
FWCI
9.92
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Nature (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, cc-by-nc)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health (1s10rr025622-01)
  • National Institute of Mental Health (U01MH124619, K99MH131832)
  • National Human Genome Research Institute (R01HG010898)
  • National Institute of Neurological Disorders and Stroke (R35NS097305, P01NS083513, R01NS028478)
  • National Center for Research Resources (S10 RR025622)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
synaptic development, postsynaptic density, neoteny, human brain evolution, dendritic spine maturation, RhoGEF, neocortex, developmental timing, synapse maturation
MeSH terms
Adolescent, Animals, Child, Child, Preschool, Cognition, Gestational Age, Humans, Infant, Infant, Newborn, Macaca, Neurons, Species Specificity, Synapses, Signal Transduction, Proteomics, Dendritic Spines, Mice, Young Adult, Post-Synaptic Density, Rho Guanine Nucleotide Exchange Factors

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