Modelling spatially regulated β-catenin dynamics and invasion in intestinal crypts

Philip J. Murray, Jun Won Kang, Gary R. Mirams, Sung Young Shin, Helen M. Byrne, Philip K. Maini, Kwang Hyun Cho

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

Abstract

Experimental data (e.g., genetic lineage and cell population studies) on intestinal crypts reveal that regulatory features of crypt behavior, such as control via morphogen gradients, are remarkably well conserved among numerous organisms (e.g., from mouse and rat to human) and throughout the different regions of the small and large intestines. In this article, we construct a partial differential equation model of a single colonic crypt that describes the spatial distribution of Wnt pathway proteins along the crypt axis. The novelty of our continuum model is that it is based upon assumptions that can be directly related to processes at the cellular and subcellular scales. We use the model to predict how the distributions of Wnt pathway proteins are affected by mutations. The model is then extended to investigate how mutant cell populations can invade neighboring crypts. The model simulations suggest that cell crowding caused by increased proliferation and decreased cell loss may be sufficient for a mutant cell population to colonize a neighboring healthy crypt.

Original languageEnglish
Pages (from-to)716-725
Number of pages10
JournalBiophysical Journal
Volume99
Issue number3
DOIs
Publication statusPublished - 4 Aug 2010

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