The Mathematical Institute, University of Oxford, Eprints Archive

Modelling hair follicle growth dynamics as an excitable medium

Murray, P J and Maini, P. K. and Plikus, M. V. and Chuong, C. M. and Baker, R. E. (2012) Modelling hair follicle growth dynamics as an excitable medium. PLOs Computational Biology, 8 (12). e1002804-(19 pages).

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The hair follicle system represents a tractable model for the study of stem cell behaviour in regenerative adult epithelial tissue. However, although there are numerous spatial scales of observation (molecular, cellular, follicle and multi follicle), it is not yet clear what mechanisms underpin the follicle growth cycle. In this study we seek to address this problem by describing how the growth dynamics of a large population of follicles can be treated as a classical excitable medium. Defining caricature interactions at the molecular scale and treating a single follicle as a functional unit, a minimal model is proposed in which the follicle growth cycle is an emergent phenomenon. Expressions are derived, in terms of parameters representing molecular regulation, for the time spent in the different functional phases of the cycle, a formalism that allows the model to be directly compared with a previous cellular automaton model and experimental measurements made at the single follicle scale. A multi follicle model is constructed and numerical simulations are used to demonstrate excellent qualitative agreement with a range of experimental observations. Notably, the excitable medium equations exhibit a wider family of solutions than the previous work and we demonstrate how parameter changes representing altered molecular regulation can explain perturbed patterns in Wnt over-expression and BMP down-regulation mouse models. Further experimental scenarios that could be used to test the fundamental premise of the model are suggested. The key conclusion from our work is that positive and negative regulatory interactions between activators and inhibitors can give rise to a range of experimentally observed phenomena at the follicle and multi follicle spatial scales and, as such, could represent a core mechanism underlying hair follicle growth.

Item Type:Article
Subjects:A - C > Biology and other natural sciences
Research Groups:Centre for Mathematical Biology
ID Code:1649
Deposited By: Philip Maini
Deposited On:10 Jan 2013 08:41
Last Modified:29 May 2015 19:20

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