TY - JOUR
T1 - A cross-species proteomic map reveals neoteny of human synapse development
AU - Wang, Li
AU - Pang, Kaifang
AU - Zhou, Li
AU - Cebrián-Silla, Arantxa
AU - González-Granero, Susana
AU - Wang, Shaohui
AU - Bi, Qiuli
AU - White, Matthew L.
AU - Ho, Brandon
AU - Li, Jiani
AU - Li, Tao
AU - Perez, Yonatan
AU - Huang, Eric J.
AU - Winkler, Ethan A.
AU - Paredes, Mercedes F.
AU - Kovner, Rothem
AU - Sestan, Nenad
AU - Pollen, Alex A.
AU - Liu, Pengyuan
AU - Li, Jingjing
AU - Piao, Xianhua
AU - García-Verdugo, José Manuel
AU - Alvarez-Buylla, Arturo
AU - Liu, Zhandong
AU - Kriegstein, Arnold R.
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/10/5
Y1 - 2023/10/5
N2 - The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood 1,2. 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.
AB - The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood 1,2. 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.
UR - http://www.scopus.com/inward/record.url?scp=85171279615&partnerID=8YFLogxK
U2 - 10.1038/s41586-023-06542-2
DO - 10.1038/s41586-023-06542-2
M3 - Article
C2 - 37704727
AN - SCOPUS:85171279615
SN - 0028-0836
VL - 622
SP - 112
EP - 119
JO - Nature
JF - Nature
IS - 7981
ER -