Computational investigation of mechanical mechanisms underlying diverse cerebellar lobular morphologies.

The mammalian cerebellum is a densely folded structure composed of lobules separated by deep fissures, while individual lobules display striking diversity in shape and size. Although multicellular processes such as granule cell proliferation and migration drive cerebellar morphogenesis, mechanical mechanisms that generate diverse lobular morphologies after initial folding remain poorly understood. Spatially heterogeneous cortical growth arising from multicellular dynamics is considered critical for the formation of characteristic lobular morphologies. In this study, we employed mathematical modeling and computer simulations to investigate how heterogeneous cortical growth influences cerebellar lobular morphology. We developed a mathematical model of cerebellar cortical growth based on continuum mechanics and simulated lobular deformation under spatially heterogeneous cortical growth using the finite element method. Our simulations indicated that heterogeneous cortical growth modulates the rates of increase in lobular height and width; however, under most conditions, lobules elongate during cortical growth, forming columnar morphologies because of the strong constraints imposed by anchoring centers, i.e., the bases of the initial fissures. In contrast, fan-shaped lobules emerged only when relatively large cortical growth occurred in a flat cortical region at the lobular apex, resulting in expansion along the anterior-posterior axis. These results confirm that the interplay between spatially heterogeneous cortical growth and initial lobular morphology is a key mechanical requirement for generating diverse cerebellar lobular morphologies, highlighting the utility of computational approaches for dissecting complex morphogenetic processes.