Divergent and combinatorial mechanical strategies that promote epithelial folding during morphogenesis

Folding is an important way by which epithelia are sculpted into three-dimensional shapes during development. Recent studies have integrated quantitative image analysis and physical modeling to uncover contributing mechanisms. It is becoming clear that folding processes often employ multiple mechanisms of force generation. Here, we review divergent modes of epithelial folding. We argue that, in many cases, several mechanisms interact at different time-scales and length-scales to generate a fold. In other cases, very similar folds are generated by different folding mechanisms. How one (or a specific combination of) mechanism(s) might be advantageous in one case versus another is not understood, and future work using quantitative analyses and modeling will be required to determine reasons for distinct modes of folding.