Wetting Dynamics and Somite Pattern Formation in Human in vitro Somitogenesis

Somite formation is a fundamental morphogenetic process that segments the presomitic mesoderm and establishes the vertebrate body plan. While the genetic and molecular cues underlying this process are well characterized, the physical mechanisms driving somite segmentation remain less understood. Here, we investigate the physical basis of somite patterning using human iPSC-derived 2.5D somitoids—somite-like organoids that recapitulate the temporal dynamics of somitogenesis. We identify a regime of dewetting–wetting transitions (tissue-scale contraction) and fracture-like behavior that underlies somite formation in somitoids. Crack initiate as cells start to form islands of higher density within a less dense cells; Over time, these larger islands split into smaller, rosette-like structures. Unlike the drying of mud, somite fracture initiates at the substrate-facing surface and propagates upward. By tuning the substrate stiffness, we observe smaller somite pattern on stiffer substrate. Concurrently, a mesenchymal-to-epithelial transition (MET) drives apical actin and N-cadherin accumulation, forming macrocellular rosette structures that orient and elongate cells while reduce cell migration. Perturbation of actin polymerization or myosin II activity abolishes actin rosettes and prevents somite pattern formation. Together, these results reveal that fluid-to-solid transitions, tissue contraction, and substrate-dependent fracture dynamics cooperate to shape somite patterning in vitro. This work provides a physical framework for vertebrate segmentation and suggests that mechanical dysregulation may contribute to developmental disorders.