Modelling spatially regulated beta-catenin dynamics and invasion in intestinal crypts.
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.
Murray
Philip J
PJ
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. murrayp@maths.ox.ac.uk
Kang
Jun-Won
JW
Mirams
Gary R
GR
Shin
Sung-Young
SY
Byrne
Helen M
HM
Maini
Philip K
PK
Cho
Kwang-Hyun
KH
D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D051379:Mice; D008871:Microvilli / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D050505:Mutant Proteins; D051153:Wnt Proteins; D051176:beta Catenin