We discovered expression of SYNGAP1, which encodes the ‘synaptic’ protein SYNGAP1, within human cortical progenitors. In an organoid model of SYNGAP1 haploinsufficiency, cortical neurogenesis and neuronal network activity were disrupted. This finding reveals an unknown function for SYNGAP1 at early stages of development, providing a new framework for understanding the pathophysiology of autism spectrum disorder.
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References
Bourgeron, T. From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat. Rev. Neurosci. 16, 551–563 (2015). This review presents an overview of the genetic architecture of ASD and synaptic disruption in cellular and animal models.
Urenda, J. P. et al. Present and future modeling of psychiatric connectopathies with brain organoids. Biol. Psychiatry. 93, 606–615 (2023). This review discusses brain organoids as a tool for modeling cellular aspects of neuropsychiatric disorders.
Agarwal, M., Johnston, M. V. & Stafstrom, C. E. SYNGAP1 mutations: clinical, genetic, and pathophysiological features. Int. J. Dev. Neurosci. 78, 65–76 (2019). This review describes clinical and pathophysiological effects of SYNGAP1 mutations, with a focus on synaptogenesis, neural circuit function and cellular plasticity.
Willsey, H. R. et al. Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience. Neuron 109, 788–804 (2021). This paper uses Xenopus tropicalis as a model system to study the effect of loss-of-function variants in ten top ASD-associated genes, and identified an increase in the ratio of neural progenitors to mature neurons as a convergent mechanism.
Atamian, A., Cordón-Barris, L. & Quadrato, G. Taming human brain organoids one cell at a time. Semin. Cell Dev. Biol. 111, 23–31 (2021). This review highlights emerging technologies combining RNA sequencing with functional, spatial, and lineage information to deconvolute brain organoids.
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This is a summary of: Birtele, M. et al. Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis. Nature https://doi.org/10.1038/s41593-023-01477-3 (2023).
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Discovery of a non-canonical function of SYNGAP1 at early stages of human cortical neurogenesis. Nat Neurosci 26, 2050–2051 (2023). https://doi.org/10.1038/s41593-023-01486-2
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DOI: https://doi.org/10.1038/s41593-023-01486-2
