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A full lifespan model of vertebrate lens growth

The mathematical determinants of vertebrate organ growth have yet to be elucidated fully. Here, we utilized empirical measurements and a dynamic branching process-based model to examine the growth of a simple organ system, the mouse lens, from E14.5 until the end of life. Our stochastic model used d...

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Autores principales: Šikić, Hrvoje, Shi, Yanrong, Lubura, Snježana, Bassnett, Steven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society Publishing 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319337/
https://www.ncbi.nlm.nih.gov/pubmed/28280571
http://dx.doi.org/10.1098/rsos.160695
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author Šikić, Hrvoje
Shi, Yanrong
Lubura, Snježana
Bassnett, Steven
author_facet Šikić, Hrvoje
Shi, Yanrong
Lubura, Snježana
Bassnett, Steven
author_sort Šikić, Hrvoje
collection PubMed
description The mathematical determinants of vertebrate organ growth have yet to be elucidated fully. Here, we utilized empirical measurements and a dynamic branching process-based model to examine the growth of a simple organ system, the mouse lens, from E14.5 until the end of life. Our stochastic model used difference equations to model immigration and emigration between zones of the lens epithelium and included some deterministic elements, such as cellular footprint area. We found that the epithelial cell cycle was shortened significantly in the embryo, facilitating the rapid growth that marks early lens development. As development progressed, epithelial cell division becomes non-uniform and four zones, each with a characteristic proliferation rate, could be discerned. Adjustment of two model parameters, proliferation rate and rate of change in cellular footprint area, was sufficient to specify all growth trajectories. Modelling suggested that the direction of cellular migration across zonal boundaries was sensitive to footprint area, a phenomenon that may isolate specific cell populations. Model runs consisted of more than 1000 iterations, in each of which the stochastic behaviour of thousands of cells was followed. Nevertheless, sequential runs were almost superimposable. This remarkable degree of precision was attributed, in part, to the presence of non-mitotic flanking regions, which constituted a path by which epithelial cells could escape the growth process. Spatial modelling suggested that clonal clusters of about 50 cells are produced during migration and that transit times lengthen significantly at later stages, findings with implications for the formation of certain types of cataract.
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spelling pubmed-53193372017-03-09 A full lifespan model of vertebrate lens growth Šikić, Hrvoje Shi, Yanrong Lubura, Snježana Bassnett, Steven R Soc Open Sci Cellular and Molecular Biology The mathematical determinants of vertebrate organ growth have yet to be elucidated fully. Here, we utilized empirical measurements and a dynamic branching process-based model to examine the growth of a simple organ system, the mouse lens, from E14.5 until the end of life. Our stochastic model used difference equations to model immigration and emigration between zones of the lens epithelium and included some deterministic elements, such as cellular footprint area. We found that the epithelial cell cycle was shortened significantly in the embryo, facilitating the rapid growth that marks early lens development. As development progressed, epithelial cell division becomes non-uniform and four zones, each with a characteristic proliferation rate, could be discerned. Adjustment of two model parameters, proliferation rate and rate of change in cellular footprint area, was sufficient to specify all growth trajectories. Modelling suggested that the direction of cellular migration across zonal boundaries was sensitive to footprint area, a phenomenon that may isolate specific cell populations. Model runs consisted of more than 1000 iterations, in each of which the stochastic behaviour of thousands of cells was followed. Nevertheless, sequential runs were almost superimposable. This remarkable degree of precision was attributed, in part, to the presence of non-mitotic flanking regions, which constituted a path by which epithelial cells could escape the growth process. Spatial modelling suggested that clonal clusters of about 50 cells are produced during migration and that transit times lengthen significantly at later stages, findings with implications for the formation of certain types of cataract. The Royal Society Publishing 2017-01-18 /pmc/articles/PMC5319337/ /pubmed/28280571 http://dx.doi.org/10.1098/rsos.160695 Text en © 2017 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Cellular and Molecular Biology
Šikić, Hrvoje
Shi, Yanrong
Lubura, Snježana
Bassnett, Steven
A full lifespan model of vertebrate lens growth
title A full lifespan model of vertebrate lens growth
title_full A full lifespan model of vertebrate lens growth
title_fullStr A full lifespan model of vertebrate lens growth
title_full_unstemmed A full lifespan model of vertebrate lens growth
title_short A full lifespan model of vertebrate lens growth
title_sort full lifespan model of vertebrate lens growth
topic Cellular and Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319337/
https://www.ncbi.nlm.nih.gov/pubmed/28280571
http://dx.doi.org/10.1098/rsos.160695
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