Ectodermal origins of the skin-brain axis: a novel model for the developing brain, inflammation, and neurodevelopmental conditions

Early life development and its divergence is influenced by multiple genetic, neurological, and environmental factors. Atypical neurodevelopment, such as that observed in autism spectrum disorder, likely begins in early gestation during a period of entwined growth between the brain and epithelial barriers of the skin, gastrointestinal tract, and airway. This review coalesces epidemiological and neuroinflammatory evidence linking cutaneous atopic disease with both reduced skin barrier integrity and determinants of neurodivergence. We consider the shared developmental origin of epidermal and neural tissue with related genetic and environmental risk factors to evaluate potential pre- and postnatal modifiers of the skin-brain connection. Initial postnatal skin barrier integrity may provide a useful marker for both cortical integrity and meaningful subgroups of children showing early neurodevelopmental delays. It may also modify known risk factors to neurodevelopment, such as pathogen caused immune system activation. These novel insights of a skin-brain-neurodevelopment connection may advance detection and intervention opportunities.