MAPPING CELLULAR AND MOLECULAR LANDSCAPES OF CORTICAL FOLDING

The cerebral cortex underlies higher cognitive functions in mammals, and its characteristic folding is closely linked to both normal brain function and neurodevelopmental disorders. Despite its clinical relevance, the mechanisms driving cortical folding remain incompletely understood. Although numerous studies have identified molecular, cellular, and mechanical processes involved in cortical folding, these factors are typically examined in isolation. Our project aims to integrate these perspectives and elucidate how their dynamic interactions shape cortical folding during development.
To this end, we systematically map cortical cell types, gene expression patterns, and proliferative dynamics across developmental stages and species. Using serial cryosections combined with immunofluorescence, high-resolution slide scanning, and three-dimensional reconstruction, we generate spatially resolved maps of cortical cell populations in developing mouse and human brains. These maps are integrated with single-nucleus transcriptomic profiling of defined cortical regions and layers to capture molecular gradients underlying cortical patterning.
In parallel, we quantify progenitor proliferation and mitotic activity across the developing forebrain to identify species-specific differences in growth dynamics that precede and accompany cortical folding. Together, these multiscale datasets provide a unified framework linking cell identity, gene expression, and growth patterns to emerging cortical geometry. By integrating these biological data with mechanical modeling, our project seeks to move beyond descriptive models and identify the principles by which molecular, cellular, and mechanical processes interact to shape cortical architecture and function.