DECODING THE MECHANICAL BASIS OF CORTICAL MORPHOGENESIS

Cortical folding generates the characteristic gyri and sulci of the mammalian brain, and it emerges from the coordinated interactions between rapid tissue growth, mechanical constraints and cellular organization. While traditional models of cortical development emphasize biochemical signalling pathways that direct proliferation, migration and differentiation, mechanical forces such as tension, compression and shear are increasingly recognized as key regulators of these processes. Mechanical cues modulate how cells interpret molecular signals, creating a mechanochemical feedback system that influences cortical morphogenesis. In this study, we investigate the role of mechanical forces in shaping cortical architecture through integrated in vitro and in vivo approaches. Mouse and ferret models are used to capture complementary developmental contexts corresponding to lissencephalic and gyrencephalic brains, respectively. Controlled mechanical perturbations are employed to analyse how tissue-level stresses influence cellular behaviour and folding dynamics. We are conducting preliminary in vitro studies to assess how substrate mechanics affect progenitor cell proliferation, morphology, and mechanosensitive signalling, by culturing neural progenitor cells from mouse and ferret cortex on hydroxy polyacrylamide hydrogels of defined stiffness. By linking mechanical environments to cellular responses and cortical-scale geometry, we aim to elucidate the role of mechanotransduction in cortical folding. Our insights will contribute to a more comprehensive understanding of how physical and biochemical factors converge to shape brain structure during development.