ArticleMolecular psychiatry2018
Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult hippocampal neurogenesis.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Connecting DCX, COMT and FMR1 in social behavior and cognitive impairment.Behavioral and brain functions : BBF · 2022Pooled it
- Tbx1 heterozygosity in the oligodendrocyte lineage shifts myelinated axon composition in the mouse fimbria without behavioral impairments.Molecular brain · 2026Article
- Article
- Highly demarcated structural alterations in the brain and impaired social incentive learning in Tbx1 heterozygous mice.Molecular psychiatry · 2025Article
- Tbx1 haploinsufficiency leads to local skull deformity, paraflocculus and flocculus dysplasia, and motor-learning deficit in 22q11.2 deletion syndrome.Nature communications · 2024Article
- Developmental regression of novel space preference in an autism spectrum disorder model is unlinked to GABAergic and social circuitry.Frontiers in cellular neuroscience · 2024Article
- Distinct neurocognitive profiles and clinical phenotypes associated with copy number variation at the 22q11.2 locus.Autism research : official journal of the International Society for Autism Research · 2023Article
- Article
- Structural alterations in the amygdala and impaired social incentive learning in a mouse model of a genetic variant associated with neurodevelopmental disorders.Research square · 2023Article
- Distinct Neurocognitive Profiles and Clinical Phenotypes Associated with Copy Number Variation at the 22q11.2 Locus.medRxiv : the preprint server for health sciences · 2023Article
- Implication of Hippocampal Neurogenesis in Autism Spectrum Disorder: Pathogenesis and Therapeutic Implications.Current neuropharmacology · 2023Review
- Tbx1, a gene encoded in 22q11.2 copy number variant, is a link between alterations in fimbria myelination and cognitive speed in mice.Molecular psychiatry · 2022Article
- Article
- Computational identification of variables in neonatal vocalizations predictive for postpubertal social behaviors in a mouse model of 16p11.2 deletion.Molecular psychiatry · 2021Article
- Heterozygosity of murine Crkl does not recapitulate behavioral dimensions of human 22q11.2 hemizygosity.Genes, brain, and behavior · 2021Article
- Reciprocal Copy Number Variations at 22q11.2 Produce Distinct and Convergent Neurobehavioral Impairments Relevant for Schizophrenia and Autism Spectrum Disorder.Biological psychiatry · 2020Article
- Assessing auditory processing endophenotypes associated with Schizophrenia in individuals with 22q11.2 deletion syndrome.Translational psychiatry · 2020Article
- Association of genetic variants at 22q11.2 chromosomal region with cognitive performance in Japanese patients with schizophrenia.Schizophrenia research. Cognition · 2019Article
- Modeling and Predicting Developmental Trajectories of Neuropsychiatric Dimensions Associated With Copy Number Variations.The international journal of neuropsychopharmacology · 2019Review
- Critical reappraisal of mechanistic links of copy number variants to dimensional constructs of neuropsychiatric disorders in mouse models.Psychiatry and clinical neurosciences · 2018Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.
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