Svenja K. Müller, Rahul N. Acharya, Mingyi Zhang
Morphogenesis, the biological process that causes an organism to develop its shape, is a crucial aspect of developmental biology. This study aims to elucidate the integrative mechanisms underlying epithelial folding, a fundamental morphogenetic process in vertebrates. Employing a combination of live imaging, genetic manipulation, and computational modeling, we investigated the role of the cytoskeletal elements and cell adhesion molecules in epithelial dynamics. Our results identified a pivotal interaction between actin filaments and cadherin-based adhesions, facilitating the mechanical forces necessary for tissue invagination. Specifically, perturbation of actin polymerization disrupted epithelial folding in zebrafish embryos, reducing folding efficiency by 45% (p < 0.01). Furthermore, computational models validated our empirical findings, showing that an optimal balance between cellular contractility and adhesion strength is required for precise morphogenetic outcomes. These findings highlight the complexity of tissue morphogenesis and suggest potential pathways for investigating congenital disorders associated with morphogenetic defects. In conclusion, our study provides a comprehensive understanding of the molecular and biophysical mechanisms driving epithelial folding, offering insights into fundamental developmental processes.