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Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism

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Published on: October 17, 2025

Spatial architecture of autism pathogenesis reveals mosaic structural disarray during early development.

Li Lin¹, Tzuen Yih Saw², Nigel Chou²

¹Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.

Nature Communications

|June 13, 2026

Summary

Autism spectrum disorder (ASD) pathogenesis involves spatially disorganized prenatal brain development. This mosaic pattern of abnormalities contributes to the diverse symptoms and brain variations seen in ASD patients.

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Area of Science:

Neuroscience
Developmental Biology
Genetics

Background:

Autism spectrum disorder (ASD) is linked to genetic and molecular factors, but its developmental origins and contribution to clinical heterogeneity are not fully understood.
Understanding the early stages of ASD pathophysiology is crucial for explaining the wide range of clinical presentations.

Purpose of the Study:

To map the spatial architecture of ASD pathogenesis in the prenatal cortex.
To investigate how molecular and genetic factors contribute to spatial disorganization during early brain development in ASD.

Main Methods:

Utilized spatial and single-cell transcriptomics.
Analyzed genetically diverse patient-derived organoids of the prenatal cortex.

Main Results:

Identified abnormal partitioning of progenitor and neuron zones in ASD organoids.
Observed localized patches of disorganized neurons with patient-specific distributions.
Found that this spatial disarray persists into neuronal maturation, suggesting impaired progenitor cell adhesion.

Conclusions:

The spatial landscape of biological processes in ASD pathogenesis is highly heterogeneous.
A model of spatially mosaic pathogenesis during prenatal development explains ASD's clinical heterogeneity and brain structure variations.