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Article Dans Une Revue Scientific Reports Année : 2019

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

Anne Danckaert
Jean-Yves Tinevez

Résumé

The synaptic protein SHANK3 encodes a multidomain scafold protein expressed at the postsynaptic density of neuronal excitatory synapses. We previously identifed 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 diferentiation of neural stem cells, dendritic spines from pyramidal neurons presented variable morphologies: flopodia, thin, stubby and muschroom, as measured in 3D using GFP labeling and immunofuorescence. As compared to three controls, we observed a signifcant decrease in SHANK3 mRNA levels (less than 50% of controls) in correlation with a signifcant 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.
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hal-02010139 , version 1 (06-02-2019)

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Laura Gouder, Aline Vitrac, Hany Goubran-Botros, Anne Danckaert, Jean-Yves Tinevez, et al.. Altered spinogenesis in iPSC-derived cortical neurons from patients with autism carrying de novo SHANK3 mutations. Scientific Reports, 2019, 9 (1), pp.1-11. ⟨10.1038/s41598-018-36993-x⟩. ⟨hal-02010139⟩
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