Epithelial organs such as the lungs, kidneys and mammary glands achieve their tree-like architecture through a process known as branching morphogenesis.

The mechanisms by which the branching patterns form are unknown. A recent study identified variations in the concentration of inhibitory chemicals, determined by the geometry of the tissue, as a factor in the patterning of the mammary gland. Our group implicated mechanical stress, which also depends upon tissue geometry, as another regulator of the process.

We used micropatterning techniques to generate mouse mammary tissue shaped in a spiral and embedded in a 3-D collagen gel. This spiral geometry imposes contradictory branching cues on the cells: high stress and high concentration at the center. The cells are confused. Which cue will they follow? Will they branch or not? The nuclei of the cells (in red) and the phase contrast image are superimposed.