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

Authors :
Wang L
Pang K
Zhou L
Cebrián-Silla A
González-Granero S
Wang S
Bi Q
White ML
Ho B
Li J
Li T
Perez Y
Huang EJ
Winkler EA
Paredes MF
Kovner R
Sestan N
Pollen AA
Liu P
Li J
Piao X
García-Verdugo JM
Alvarez-Buylla A
Liu Z
Kriegstein AR
Source :
Nature [Nature] 2023 Oct; Vol. 622 (7981), pp. 112-119. Date of Electronic Publication: 2023 Sep 13.
Publication Year :
2023

Abstract

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood <superscript>1,2</superscript> . Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that human PSDs mature about two to three times slower than those of other species and contain higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of RhoGEF signalling in human neurons delays morphological maturation of dendritic spines and 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. Our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation.<br /> (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Details

Language :
English
ISSN :
1476-4687
Volume :
622
Issue :
7981
Database :
MEDLINE
Journal :
Nature
Publication Type :
Academic Journal
Accession number :
37704727
Full Text :
https://doi.org/10.1038/s41586-023-06542-2