Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.
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.
Gut Health and Food Safety Research Programme, Institute of Food Research, Norwich, United Kingdom.
Aimee
A
Parker
Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom.
Oliver J
OJ
Maclaren
Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom.|School of Mathematics and Statistics, University of Sheffield, Sheffield, United Kingdom.|Bateson Centre, University of Sheffield, Sheffield, United Kingdom.
Alexander G
AG
Fletcher
Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom.
Daniele
D
Muraro
Department of Biochemistry, University of Cambridge, United Kingdom; and.
Peter A
PA
Kreuzaler
Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom.
Helen M
HM
Byrne
Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom.
Philip K
PK
Maini
Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
Alastair J M
AJ
Watson
Gut Health and Food Safety Research Programme, Institute of Food Research, Norwich, United Kingdom; carmen.pin@ifr.ac.uk.
Carmen
C
Pin
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D003561:Cytarabine / Q000494:pharmacology; D005260:Female; D007421:Intestine, Small / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine
epithelium; mathematical model; small intestine