Convergent Cortical Development Delays Across Autism Mouse Models
A large multi-omics study profiling 251 samples from 11 ASD-linked mouse models across embryonic and postnatal stages, both sexes, and two brain regions finds convergence on disruptions to the radial glial lineage that manifest as a transient developmental delay rather than lasting lineage mis-specification. Neurons show the largest early postnatal transcriptional changes, including downregulation of synaptic and ion-channel genes consistent with delayed maturation. Within each developmental window, models converge on shared molecular programs, but the convergence diminishes by postnatal day 14, with cross-genotype heterogeneity overlaying stage-specific effects. Electrophysiology corroborates altered neuronal excitability and synaptic properties across models, and sex-specific gene expression differences emerge, often with larger effects in females. Using multiplexed snRNA-seq/snATAC-seq (snMultiome), EdU lineage tracing, RNAscope, and biophysical modeling, the study maps developmental trajectories and cross-model convergence, offering a unified view of how diverse ASD mutations perturb cortical development.
