Cell shape and fate changes in 3D model of mammalian hair follicle development*

During mammalian skin development, a subset of basal cells within the epithelial compartment will alter their fate to specify into hair follicle cells. This collection of cells will compartmentalize, elongate and invaginate into the connective tissue under the epithelial layer to form a structure termed the placode. We investigate two possible mechanisms that might trigger this transition using an extended 3D Vertex model with features specific to skin, including additional heterotypic tension at interfaces between cells of different types. The first mechanism involves placode cells executing cell-autonomous changes in cell mechanics, e.g. altering myosin activity near the cortex or expression/localization of cell-cell adhesion molecules. A second mechanism involves a ring of fibroblast cells around the placode generating contractile forces which trigger the cell fate changes. We find both mechanisms can trigger elongation and invagination, and by quantitatively comparing model predictions for the placode's geometric and dynamic behavior to experiments we isolate the dominant mechanism at different developmental stages.