Computational models reveal a passive mechanism for cell migration in the crypt.

Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active mov...

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Main Authors: Sara-Jane Dunn, Inke S Näthke, James M Osborne
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0080516
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author Sara-Jane Dunn
Inke S Näthke
James M Osborne
author_facet Sara-Jane Dunn
Inke S Näthke
James M Osborne
author_sort Sara-Jane Dunn
collection DOAJ
description Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt.
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spelling doaj-art-0c4cd511f9b0446f848ccf43a2d508852025-08-20T03:10:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8051610.1371/journal.pone.0080516Computational models reveal a passive mechanism for cell migration in the crypt.Sara-Jane DunnInke S NäthkeJames M OsborneCell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt.https://doi.org/10.1371/journal.pone.0080516
spellingShingle Sara-Jane Dunn
Inke S Näthke
James M Osborne
Computational models reveal a passive mechanism for cell migration in the crypt.
PLoS ONE
title Computational models reveal a passive mechanism for cell migration in the crypt.
title_full Computational models reveal a passive mechanism for cell migration in the crypt.
title_fullStr Computational models reveal a passive mechanism for cell migration in the crypt.
title_full_unstemmed Computational models reveal a passive mechanism for cell migration in the crypt.
title_short Computational models reveal a passive mechanism for cell migration in the crypt.
title_sort computational models reveal a passive mechanism for cell migration in the crypt
url https://doi.org/10.1371/journal.pone.0080516
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