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Biophys. J., Volume 99, Issue 3, 716-725, 4 August 2010 | doi:10.1016/j.bpj.2010.05.016 Modelling Spatially Regulated β-Catenin Dynamics and Invasion in Intestinal Crypts

Abstract

Philip J. Murray^†,‡,*, Jun-Won Kang^{†, §}, Gary R. Mirams^¶, Sung-Young Shin^†, Helen M. Byrne^∥, Philip K. Maini^{‡, ††} and Kwang-Hyun Cho^†,*

^†Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
^‡Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom
^§Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
^¶Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
^∥Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, University of Nottingham, Nottingham, United Kingdom
^††Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom

*Corresponding author

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.

논문정보

형식Research article
게재일2010년 08월 (BRIC 등록일 )
연구진국내(교신)+국외 연구진
분야 생명과학 > 생물공학
구분구・추천논문

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