From spatial patterning to coordinated execution: a cross-system framework for autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by differences in social communication and restricted or repetitive behaviors, yet converging evidence also points to altered neural timing, synchronization, and large-scale coordination despite largely preserved gross neuroanatomy. Parallel observations across non-neural systems, including functional gastrointestinal disturbances, minor anomalies in neural crest-derived tissues, and variation in epithelial patterning outcomes, raise the possibility of a broader vulnerability in coordination-dependent biological processes. Here, we propose a framework in which developmental systems distinguish between spatial patterning mechanisms that establish tissue geometry and a calcium-dependent execution layer that stabilizes coordinated behavior across time. Patterning systems, including planar cell polarity signaling, morphogen gradients, and neural crest guidance cues, specify directional organization and spatial relationships among cells. Their realization, however, requires intracellular processes capable of synchronizing cytoskeletal remodeling, adhesion dynamics, excitability, and metabolic coupling across cells and networks. Within this framework, intracellular Ca²