The mechanism of their formation during development was recently revealed by a study published in
. The investigations, carried out by two research groups at Harvard University, were complemented by computational modelling carried out at the University of Jyväskylä and funded by the Academy of Finland.
Villification (villus formation) has previously been hypothesised to be based on an active mechanism coordinated by growth factors. The present study, however, shows that a simple mechanical compression of the epithelium sheet is all that it takes. The epithelium gets compressed mechanically as the surrounding layers of smooth muscle differentiate and grow slower than the epithelium. This compression leads to a spontaneous buckling of the epithelium first into longitudinal folds, then a zigzag pattern, and finally villi. The non-uniform distribution of growth factors and cell differentiation turned out to be a consequence - not a reason - of the complex epithelial topography.
Physicists and mathematicians had studied the mechanical surface instabilities essential to villification a few years earlier, but the theoretical results have not been applied before to explain the morphogenesis of biological structures at quantitative level. In a broader view, the study reminds us that even complex biological structures form just as a sequence of simple physical processes.