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A cross-species proteomic map reveals neoteny of human synapse development.
Wang, Li; Pang, Kaifang; Zhou, Li; Cebrián-Silla, Arantxa; González-Granero, Susana; Wang, Shaohui; Bi, Qiuli; White, Matthew L; Ho, Brandon; Li, Jiani; Li, Tao; Perez, Yonatan; Huang, Eric J; Winkler, Ethan A; Paredes, Mercedes F; Kovner, Rothem; Sestan, Nenad; Pollen, Alex A; Liu, Pengyuan; Li, Jingjing; Piao, Xianhua; García-Verdugo, José Manuel; Alvarez-Buylla, Arturo; Liu, Zhandong; Kriegstein, Arnold R.
Affiliation
  • Wang L; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA. Li.Wang@ucsf.edu.
  • Pang K; Department of Neurology, University of California San Francisco, San Francisco, CA, USA. Li.Wang@ucsf.edu.
  • Zhou L; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, USA.
  • Cebrián-Silla A; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
  • González-Granero S; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Wang S; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  • Bi Q; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • White ML; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Ho B; Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia and CIBERNED, Valencia, Spain.
  • Li J; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Li T; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  • Perez Y; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Huang EJ; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  • Winkler EA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Paredes MF; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  • Kovner R; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Sestan N; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  • Pollen AA; Gilead Sciences, Foster City, CA, USA.
  • Liu P; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Li J; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Piao X; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  • García-Verdugo JM; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Alvarez-Buylla A; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Liu Z; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Kriegstein AR; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Nature ; 622(7981): 112-119, 2023 Oct.
Article in En | MEDLINE | ID: mdl-37704727
ABSTRACT
The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood1,2. 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Synapses / Proteomics Limits: Adolescent / Adult / Animals / Child / Child, preschool / Humans / Infant / Newborn Language: En Journal: Nature Year: 2023 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Synapses / Proteomics Limits: Adolescent / Adult / Animals / Child / Child, preschool / Humans / Infant / Newborn Language: En Journal: Nature Year: 2023 Document type: Article Affiliation country: Estados Unidos