Altered spinogenesis in iPSC-derived cortical neurons from patients with autism carrying de novo SHANK3 mutations

The synaptic protein SHANK3 encodes a multidomain scaffold protein expressed at the postsynaptic density of neuronal excitatory synapses. We previously identified de novo SHANK3 mutations in patients with autism spectrum disorders (ASD) and showed that SHANK3 represents one of the major genes for AS...

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Veröffentlicht in:Scientific reports 2019-01, Vol.9 (1), p.94-94, Article 94
Hauptverfasser: Gouder, Laura, Vitrac, Aline, Goubran-Botros, Hany, Danckaert, Anne, Tinevez, Jean-Yves, André-Leroux, Gwenaëlle, Atanasova, Ekaterina, Lemière, Nathalie, Biton, Anne, Leblond, Claire S., Poulet, Aurélie, Boland, Anne, Deleuze, Jean-François, Benchoua, Alexandra, Delorme, Richard, Bourgeron, Thomas, Cloëz-Tayarani, Isabelle
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container_title Scientific reports
container_volume 9
creator Gouder, Laura
Vitrac, Aline
Goubran-Botros, Hany
Danckaert, Anne
Tinevez, Jean-Yves
André-Leroux, Gwenaëlle
Atanasova, Ekaterina
Lemière, Nathalie
Biton, Anne
Leblond, Claire S.
Poulet, Aurélie
Boland, Anne
Deleuze, Jean-François
Benchoua, Alexandra
Delorme, Richard
Bourgeron, Thomas
Cloëz-Tayarani, Isabelle
description The synaptic protein SHANK3 encodes a multidomain scaffold protein expressed at the postsynaptic density of neuronal excitatory synapses. We previously identified de novo SHANK3 mutations in patients with autism spectrum disorders (ASD) and showed that SHANK3 represents one of the major genes for ASD. Here, we analyzed the pyramidal cortical neurons derived from induced pluripotent stem cells from four patients with ASD carrying SHANK3 de novo truncating mutations. At 40–45 days after the differentiation of neural stem cells, dendritic spines from pyramidal neurons presented variable morphologies: filopodia, thin, stubby and muschroom, as measured in 3D using GFP labeling and immunofluorescence. As compared to three controls, we observed a significant decrease in SHANK3 mRNA levels (less than 50% of controls) in correlation with a significant reduction in dendritic spine densities and whole spine and spine head volumes. These results, obtained through the analysis of de novo SHANK3 mutations in the patients’ genomic background, provide further support for the presence of synaptic abnormalities in a subset of patients with ASD.
doi_str_mv 10.1038/s41598-018-36993-x
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source MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals
subjects 13/100
13/106
13/44
13/51
14/19
38
38/39
38/90
45/91
631/378/2597
631/45/500
631/80
Autism
Autistic Disorder - genetics
Autistic Disorder - pathology
Cell Differentiation
Dendrites - pathology
Dendritic spines
Filopodia
Humanities and Social Sciences
Humans
Immunofluorescence
Induced Pluripotent Stem Cells - physiology
Life Sciences
Microscopy, Fluorescence
mRNA
multidisciplinary
Mutation
Nerve Tissue Proteins - deficiency
Nerve Tissue Proteins - genetics
Neural stem cells
Pluripotency
Postsynaptic density
Pyramidal cells
Pyramidal Cells - cytology
Pyramidal Cells - pathology
Science
Science (multidisciplinary)
Sequence Deletion
Spine
Stem cells
Synapses
title Altered spinogenesis in iPSC-derived cortical neurons from patients with autism carrying de novo SHANK3 mutations
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