Tri-layer wrinkling as a mechanism for anchoring center initiation in the developing cerebellum

Abstract

During cerebellar development, anchoring centers form at the base of each fissure and remain fixed in place while the rest of the cerebellum grows outward. Cerebellar foliation has been extensively studied; yet, the mechanisms that control anchoring center initiation and position remain insufficiently understood. Here we show that a tri-layer model can predict surface wrinkling as a potential mechanism to explain anchoring center initiation and position. Motivated by the cerebellar microstructure, we model the developing cerebellum as a tri-layer system with an external molecular layer and an internal granular layer of similar stiffness and a significantly softer intermediate Purkinje cell layer. Including a weak intermediate layer proves key to predicting surface morphogenesis, even at low stiffness contrasts between the top and bottom layers. The proposed tri-layer model provides insight into the hierarchical formation of anchoring centers and establishes an essential missing link between gene expression and evolution of shape.