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Disproving Paradigms: The Rules of Morphogenesis (“Rules of Life”)

Since the 1980s, it has been assumed that the architecture of the mammary gland is defined by prealigned fibers of collagen, which were posited to serve as a template for the formation of the mammary epithelial tree. Princeton researchers tested the validity of this paradigm.

  1. Using quantitative imaging analysis of mouse mammary glands, we show that the only aligned fibers of collagen are located around the gland in the fascia, at least one layer of fat cells away from the epithelial tree.
  2. Using 3D printing approaches, we engineered tissues in which the epithelium is separated from prealigned fibers of collagen with the same distances that we measured in vivo. We found that these collagen fibers were unable to act as templates to direct the growth of the tree.
  3. Additional imaging analysis revealed that new branches in the tree are always preceded by accumulation of unaligned collagen at the future cleft site.
  4. Computational modeling revealed that stiff collagen at the future cleft site is sufficient to pattern the angle at which the epithelium bifurcates into two daughter branches.