Featured
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News & Views |
Targeting RNA opens therapeutic avenues for Timothy syndrome
A therapeutic strategy that alters gene expression in a rare and severe neurodevelopmental condition has been tested in stem-cell-based models of the disease, and has been shown to correct genetic and cellular defects.
- Silvia Velasco
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Article
| Open Access
Antisense oligonucleotide therapeutic approach for Timothy syndrome
Antisense oligonucleotides effectively decrease the inclusion of exon 8A of CACNA1C in human cells both in vitro and in rodents transplanted with human brain organoids, and a single intrathecal administration rescued both calcium changes and in vivo dendrite morphology of patient neurons.
- Xiaoyu Chen
- , Fikri Birey
- & Sergiu P. Pașca
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Technology Feature |
‘Without these tools, I’d be lost’: how generative AI aids in accessibility
A rush to place barriers around the use of artificial intelligence in academia could disproportionately affect those who stand to benefit most.
- Amanda Heidt
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Correspondence |
Autism: don’t negate the value of applied behaviour analysis
- Gina Green
- , Russell Lang
- & Jason Travers
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News Feature |
‘I am not a broken version of normal’ — autistic people argue for a stronger voice in research
Despite broader acceptance of neurodiversity, autistic advocates and scientists are still fighting for a chance to set clinical and scientific priorities.
- Emiliano Rodríguez Mega
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Article
| Open Access
Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD
RNA sequencing reveals widespread transcriptomic changes across the cerebral cortex in autism spectrum disorder, including primary sensory regions, in addition to association regions, as well as an attenuation of regional identity.
- Michael J. Gandal
- , Jillian R. Haney
- & Daniel H. Geschwind
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Article |
Autism genes converge on asynchronous development of shared neuron classes
Haploinsufficiency in three genes associated with risk of autism spectrum disorder—KMT5B, ARID1B and CHD8—in cell lines from multiple donors results in cell-type-specific asynchronous development of GABAergic neurons and cortical deep-layer excitatory projection neurons.
- Bruna Paulsen
- , Silvia Velasco
- & Paola Arlotta
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News |
High-profile autism genetics project paused amid backlash
Study aimed at collecting DNA from 10,000 autistic people and their families has drawn criticism for failing to consult the autism community.
- Katharine Sanderson
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Career Column |
How Zoom helped the neurotypical world hear my autistic voice
Anya Lawrence says pandemic videoconferencing has brought her closer to her colleagues and others in the world of science.
- Anya Lawrence
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Article |
GluD1 is a signal transduction device disguised as an ionotropic receptor
The ionotropic glutamate delta receptors GluD1 and GluD2 form distinct neurexin–cerebellin complexes that differentially regulate postsynaptic glutamate receptor activities.
- Jinye Dai
- , Christopher Patzke
- & Thomas C. Südhof
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Article |
Presymptomatic training mitigates functional deficits in a mouse model of Rett syndrome
In a mouse model of Rett syndrome, intensive training during the presymptomatic period markedly improves the performance of motor and memory tasks and delays the onset of symptoms, providing a rationale for the genetic screening of newborn babies.
- Nathan P. Achilly
- , Wei Wang
- & Huda Y. Zoghbi
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News Feature |
How gut microbes could drive brain disorders
Scientists are starting to work out how the gut microbiome can affect brain health. That might lead to better and easier treatments for brain diseases.
- Cassandra Willyard
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Article |
Patterns of de novo tandem repeat mutations and their role in autism
A bioinformatics pipeline to identify tandem repeat mutations is developed and used to characterize precise changes in repeat copy number associated with autism spectrum disorder.
- Ileena Mitra
- , Bonnie Huang
- & Melissa Gymrek
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Article |
Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA
Genomic integration of an adeno-associated virus vector in a mouse model of Angelman syndrome unsilences paternal Ube3a and rescues anatomical and behavioural phenotypes, suggesting a pathway towards the treatment of this neurodevelopmental disorder.
- Justin M. Wolter
- , Hanqian Mao
- & Mark J. Zylka
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Article |
Rescue of oxytocin response and social behaviour in a mouse model of autism
An autism-associated mutation in Nlgn3 results in impaired oxytocin signalling in dopaminergic neurons and altered social behavioural responses in mice, and treatment with an inhibitor of MAP kinase-interacting kinases rescues these phenotypes.
- Hanna Hörnberg
- , Enrique Pérez-Garci
- & Peter Scheiffele
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Article |
Genome-wide detection of tandem DNA repeats that are expanded in autism
Genome-wide analysis of tandem DNA repeats in the genomes of individuals with autism spectrum disorder and control participants reveals a strong contribution of tandem repeat expansions to the genetic aetiology and phenotypic complexity of autism spectrum disorder.
- Brett Trost
- , Worrawat Engchuan
- & Ryan K. C. Yuen
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Outlook |
Could the gut microbiome be linked to autism?
Researchers are hoping to understand whether the microbes in our guts have a role in the disorder.
- Elizabeth Svoboda
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Article |
IL-17a promotes sociability in mouse models of neurodevelopmental disorders
IL-17a induced by immune activation affects cortical neural activity and promotes social interaction in a mouse model of neurodevelopmental disorders.
- Michael Douglas Reed
- , Yeong Shin Yim
- & Gloria B. Choi
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News |
Lab-grown ‘mini brains’ produce electrical patterns that resemble those of premature babies
Structures could help researchers to study the early stages of brain development disorders, including epilepsy.
- Sara Reardon
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News |
Autism and DDT: What one million pregnancies can — and can’t — reveal
Analysis finds that prenatal exposure to the pesticide is associated with a higher risk of severe autism with intellectual impairment.
- Sara Reardon
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Article |
Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing
CPEB4 binds the mRNA of genes known to be associated with autism and shows an isoform imbalance in individuals with autism, and an equivalent imbalance in mice induces an autism-like phenotype.
- Alberto Parras
- , Héctor Anta
- & José J. Lucas
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Article |
5-HT release in nucleus accumbens rescues social deficits in mouse autism model
Stimulating the release of serotonin (5-HT) in the nucleus accumbens in wild-type mice promotes sociability, and rescues deficits in social behaviours in a mouse model of autism.
- Jessica J. Walsh
- , Daniel J. Christoffel
- & Robert C. Malenka
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Article |
Pyramidal cell regulation of interneuron survival sculpts cortical networks
Excitatory input onto inhibitory interneurons in the developing mouse cortex acts through PTEN to protect interneurons from cell death and thus regulate the balance between excitation and inhibition.
- Fong Kuan Wong
- , Kinga Bercsenyi
- & Oscar Marín
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Letter |
Kctd13 deletion reduces synaptic transmission via increased RhoA
Experimental evidence that global Kctd13 reduction leads to increased RhoA levels that reduce synaptic transmission, implicating RhoA as a potential therapeutic target for neuropsychiatric disorders associated with copy-number variants that include KCTD13.
- Christine Ochoa Escamilla
- , Irina Filonova
- & Craig M. Powell
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Letter |
Radically truncated MeCP2 rescues Rett syndrome-like neurological defects
Analysis of the minimal functional unit for MeCP2 protein shows that its function is to recruit the NCoR/SMRT co-repressor complex to methylated sites on chromatin, which may have use in designing strategies for gene therapy of Rett syndrome.
- Rebekah Tillotson
- , Jim Selfridge
- & Adrian Bird
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Editorial |
Pregnant mice illuminate risk factors that could lead to autism
Studies highlight link between immune response and unusual neural wiring.
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Article |
Reversing behavioural abnormalities in mice exposed to maternal inflammation
The authors define a specific cortical subregion of the somatosensory cortex as a critical region of dysfunction that is causal to the emergence of abnormal social and repetitive behaviours in mice exposed to maternal inflammation.
- Yeong Shin Yim
- , Ashley Park
- & Gloria B. Choi
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News |
‘Autistic’ mice make littermates less social
Mice genetically engineered to show autism-like symptoms can affect behaviour of unmodified animals when the two are kept together.
- Ben Upton
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Letter |
Infant viewing of social scenes is under genetic control and is atypical in autism
Monozygotic twins show high concordance in eye- and mouth-looking, and this behaviour is markedly reduced in toddlers with autism spectrum disorder.
- John N. Constantino
- , Stefanie Kennon-McGill
- & Warren Jones
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Books & Arts |
Neuroscience: How music meets mind
Elizabeth Hellmuth Margulis explores a study parsing how the brain makes sense of melody and harmony.
- Elizabeth Hellmuth Margulis
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News |
Cells that trim brain connections are linked to autism
A difference in brain biology between the sexes might render males most vulnerable to autism.
- Amy Maxmen
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Article |
Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1
Increasing expression of the autism-associated gene Ube3a, either alone or in combination with seizures, not only impairs sociability in mice but also reduces expression of the synaptic organizer Cbln1 in the ventral tegmental area, thus weakening glutamatergic transmission.
- Vaishnav Krishnan
- , David C. Stoppel
- & Matthew P. Anderson
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Letter |
Early brain development in infants at high risk for autism spectrum disorder
Surface area expansion from 6–12 months precedes brain overgrowth in high risk infants diagnosed with autism at 24 months and cortical features in the first year predict individual diagnostic outcomes.
- Heather Cody Hazlett
- , Hongbin Gu
- & Core H. Gu
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Letter |
Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism
Gene expression analysis in brain tissue from individuals with and without autism spectrum disorder (ASD) suggests that the transcription factor SOX5 contributes to an ASD-associated reduction in transcriptional differences between brain areas and indicates that common transcriptomic changes occur in different forms of ASD.
- Neelroop N. Parikshak
- , Vivek Swarup
- & Daniel H. Geschwind
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News |
Autism study finds early intervention has lasting effects
Some autism symptoms reduced in children six years after their parents receive communications training.
- Heidi Ledford
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Letter |
CHD8 haploinsufficiency results in autistic-like phenotypes in mice
Heterozygous Chd8 mutant mice display autistic-like behaviours and small but global changes in brain gene expression, which are associated with delays in neuronal development.
- Yuta Katayama
- , Masaaki Nishiyama
- & Keiichi I. Nakayama
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Letter |
Adult restoration of Shank3 expression rescues selective autistic-like phenotypes
Re-expression of the Shank3 gene in adult mice results in improvements in synaptic protein composition and spine density in the striatum; Shank3 also rescues autism-like features such as social interaction and grooming behaviour, and the results suggest that aspects of autism spectrum disorders may be reversible in adulthood.
- Yuan Mei
- , Patricia Monteiro
- & Guoping Feng
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Books & Arts |
Books in brief
Barbara Kiser reviews five of the week's best science picks.
- Barbara Kiser
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News |
Monkeys genetically modified to show autism symptoms
But it is unclear how well the results match the condition in humans.
- David Cyranoski
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Letter |
Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2
Lentivirus-based transgenic Macaca fascicularis monkeys are generated expressing the human MECP2 transgene in the brain, and they display behavioural alterations including changes in social interaction and increased anxiety; germline transmission of the transgene to the F1 offspring is shown, and these monkeys also had an altered social interaction phenotype.
- Zhen Liu
- , Xiao Li
- & Zilong Qiu
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News & Views |
A molecular tightrope
The identification of a regulatory site on the UBE3A protein that can be phosphorylated to alter its enzymatic activity provides insight into the aetiology of two human neurodevelopmental diseases, Angelman syndrome and autism.
- Ype Elgersma
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Books & Arts |
Seeing the spectrum entire
Chris Gunter examines a comprehensive history of the science and culture surrounding autism studies.
- Chris Gunter
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Brief Communications Arising |
Wild-type microglia do not reverse pathology in mouse models of Rett syndrome
- Jieqi Wang
- , Jan Eike Wegener
- & Andrew A. Pieper
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Article |
Loss of δ-catenin function in severe autism
In severe autism, deleterious variants at conserved residues are enriched in patients arising from female-enriched multiplex families, enhancing the detection of key autism genes in modest numbers of cases.
- Tychele N. Turner
- , Kamal Sharma
- & Aravinda Chakravarti
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Article |
The contribution of de novo coding mutations to autism spectrum disorder
Family-based exome sequencing in a large autism study has identified 27 high-confidence gene targets and accurately estimates the contribution of both de novo gene-disrupting and missense mutations to the incidence of simplex autism, with target genes in affected females overlapping those in males of lower but not higher IQ; targets also overlap known targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes.
- Ivan Iossifov
- , Brian J. O’Roak
- & Michael Wigler
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Article |
Synaptic, transcriptional and chromatin genes disrupted in autism
Whole-exome sequencing in a large autism study identifies over 100 autosomal genes that are likely to affect risk for the disorder; these genes, which show unusual evolutionary constraint against mutations, carry de novo loss-of-function mutations in over 5% of autistic subjects and many function in synaptic, transcriptional and chromatin-remodelling pathways.
- Silvia De Rubeis
- , Xin He
- & Joseph D. Buxbaum
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Letter |
Attention to eyes is present but in decline in 2–6-month-old infants later diagnosed with autism
A prospective longitudinal study identifies the earliest known indicator of social disability in human infancy: decline in attention to others’ eyes in infants who are later diagnosed with autism; the decline is evident already within the first 2 to 6 months of life, which reveals the early unfolding of the disorder but also offers a promising opportunity for the future of early intervention.
- Warren Jones
- & Ami Klin
Autistic people three times more likely to develop Parkinson’s-like symptoms