title: Overproduction of upper-layer neurons in the neocortex leads to autism-like features in mice.
abstract: The functional integrity of the neocortex depends upon proper numbers of excitatory and inhibitory neurons; however, the consequences of dysregulated neuronal production during the development of the neocortex are unclear. As excess cortical neurons are linked to the neurodevelopmental disorder autism, we investigated whether the overproduction of neurons leads to neocortical malformation and malfunction in mice. We experimentally increased the number of pyramidal neurons in the upper neocortical layers by using the small molecule XAV939 to expand the intermediate progenitor population. The resultant overpopulation of neurons perturbs development of dendrites and spines of excitatory neurons and alters the laminar distribution of interneurons. Furthermore, these phenotypic changes are accompanied by dysregulated excitatory and inhibitory synaptic connection and balance. Importantly, these mice exhibit behavioral abnormalities resembling those of human autism. Thus, our findings collectively suggest a causal relationship between neuronal overproduction and autism-like features, providing developmental insights into the etiology of autism.
authors.affiliation: Division of Life Science, Center for Stem Cell Research, Molecular Neuroscience Center, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Fang
authors.affiliation: Division of Life Science, Center for Stem Cell Research, Molecular Neuroscience Center, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Centre for Cell and Developmental Biology and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Division of Life Science, Center for Stem Cell Research, Molecular Neuroscience Center, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Wing-Ho
authors.initials: WH
authors.lastname: Yung
authors.affiliation: Division of Life Science, Center for Stem Cell Research, Molecular Neuroscience Center, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Amy K Y
authors.initials: AKY
authors.lastname: Fu
authors.affiliation: Division of Life Science, Center for Stem Cell Research, Molecular Neuroscience Center, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. Electronic address: boip@ust.hk.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000209:etiology / Q000473:pathology*; D049109:Cell Proliferation; D049229:Dendritic Spines / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D008297:Male; D051379:Mice; D019579:Neocortex / Q000473:pathology*; D013569:Synapses / Q000502:physiology