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

Parker, Aimee, Maclaren, Oliver J., Fletcher, Alexander G., Muraro, Daniele, Kreuzaler, Peter A., Byrne, Helen M., Maini, Philip K., Watson, Alastair J. M. and Pin, Carmen (2017) Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi. The FASEB Journal, 31 (2). pp. 636-649. ISSN 0892-6638

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Abstract

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 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 and when it is temporarily halted. We found 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 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.

Item Type: Article
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: mathematical model,epithelium,small intestine
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: Pure Connector
Date Deposited: 12 Oct 2016 09:00
Last Modified: 06 Nov 2019 16:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/60859
DOI: 10.1096/fj.201601002

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