Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi

Abstract

The functional integrity of the intestinal epithelial barrier relies on tight coordination of cellproliferation andmigration, with failure to regulate these processes resulting in disease. It is notknownwhether cell proliferation is sufficient to drive epithelial cell migration during homoeostatic turnover of the epithelium. Nor is it known precisely how villus cell migration is affected when proliferation is perturbed. Some reports suggest that proliferation and migration may not be related while other studies support a direct relationship. We used established cell-tracking methods based on thymine analog cell labeling and developed tailored mathematical models to quantify cell proliferation and migration under normal conditions and when proliferation is reduced andwhen it is temporarily halted.We found that epithelial cellmigration velocities along the villi are coupled to cell proliferation rateswithin the crypts inall conditions. Furthermore, halting and resuming proliferation results in the synchronized response of cellmigration on the villi. We conclude that cell proliferation within the crypt is the primary force that drives cell migration along the villus.Thismethodology can be applied to interrogate intestinal epithelial dynamics and characterize situations in which processes involved in cell turnover become uncoupled, including pharmacological treatments and disease models.-Parker, A., Maclaren, O. J., Fletcher, A. G., Muraro, D., Kreuzaler, P. A., Byrne, H. M., Maini, P. K., Watson, A. J.M., Pin, C. Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.