Planar Differential Growth Rates Initiate Precise Fold Positions in Complex Epithelia

• Published in: Developmental cell Vol. 51; no. 3; pp. 299 - 312.e4
• Main Authors: Tozluoǧlu, Melda, Duda, Maria, Kirkland, Natalie J., Barrientos, Ricardo, Burden, Jemima J., Muñoz, José J., Mao, Yanlan
• Format: Journal Article Publication
• Language: English
• Published: United States Elsevier Inc 04.11.2019; Cell Press
• Subjects: Animals; Basement Membrane - ultrastructure; Clone Cells; computational modeling; Computational modelling; Computer science; Computer Simulation; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Epithelium - anatomy & histology; Epithelium - growth & development; Epithelium - ultrastructure; Finite element; Folding; Imaginal Discs - anatomy & histology; Imaginal Discs - ultrastructure; Informàtica; Matemàtica; Matemàtiques i estadística; Mathematics; Models, Biological; Morphogenesis; Mutation - genetics; Time Factors; Tissue mechanics; Wings, Animal - anatomy & histology; Wings, Animal - ultrastructure; Wnt1 Protein - genetics; Àrees temàtiques de la UPC; morphogenesis; computational modeling; finite element; tissue mechanics; folding
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2019.09.009

Tissue folding is a fundamental process that shapes epithelia into complex 3D organs. The initial positioning of folds is the foundation for the emergence of correct tissue morphology. Mechanisms forming individual folds have been studied, but the precise positioning of folds in complex, multi-folded epithelia is less well-understood. We present a computational model of morphogenesis, encompassing local differential growth and tissue mechanics, to investigate tissue fold positioning. We use the Drosophila wing disc as our model system and show that there is spatial-temporal heterogeneity in its planar growth rates. This differential growth, especially at the early stages of development, is the main driver for fold positioning. Increased apical layer stiffness and confinement by the basement membrane drive fold formation but influence positioning to a lesser degree. The model successfully predicts the in vivo morphology of overgrowth clones and wingless mutants via perturbations solely on planar differential growth in silico. [Display omitted] •Drosophila wing discs grow with spatial and temporal heterogeneity•This differential growth determines the positions of epithelial folds•Constriction from the basement membrane is necessary for correct fold initiation•Our computational model correctly predicts the shape of growth mutants Like an origami crane forming from the folds of a paper, the precise positioning of multiple folds in epithelia is key for the final shape of a tissue. Tozluoǧlu et al. present a computational model that explains how precise fold positioning can be predicted by heterogeneous growth in epithelia.