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

Journal article

The functional integrity of the intestinal epithelial barrier relies on tight coordination of cell proliferation and migration, with failure to regulate these processes resulting in disease. It is not known whether 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 use established cell tracking methods based on thymine analogue cell labelling and develop tailored mathematical models to quantify cell proliferation and migration under normal conditions, when proliferation is reduced, and when it is temporarily halted. We find that epithelial cell migration velocities along the villi are coupled to cell proliferation rates within the crypts in all conditions. Furthermore, halting and resuming proliferation results in the synchronized response of cell migration on the villi. We conclude that cell proliferation within the crypt is the primary force that drives cell migration along the villus. This methodology can be applied to interrogate intestinal epithelial dynamics and characterise situations in which processes involved in cell turnover become uncoupled, including pharmacological treatments and disease models.

Authors: Parker, A; MacLaren, O; Fletcher, A; Muraro, D; Kreuzaler, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Federation of American Society of Experimental Biology
• Journal: FASEB Journal
• Volume: 31
• Issue: 2
• Pages: 636-649
• Publication date: 2016-01-01
• Acceptance date: 2016-10-11
• DOI: 10.1096/fj.201601002
• EISSN: 1530-6860
• ISSN: 0892-6638
• Keywords: mathematical model; epithelium; villus; crypt; migration; small intestine; proliferation