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Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches

Organogenesis is the phase of embryonic development leading to the formation of fully functional organs. In the case of the thyroid, organogenesis starts from the endoderm and generates a multitude of closely packed independent spherical follicular units surrounded by a dense network of capillaries....

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Autores principales: Gonay, Leolo, Spourquet, Catherine, Baudoin, Matthieu, Lepers, Ludovic, Lemoine, Pascale, Fletcher, Alexander G., Hanert, Emmanuel, Pierreux, Christophe E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216395/
https://www.ncbi.nlm.nih.gov/pubmed/34163435
http://dx.doi.org/10.3389/fendo.2021.655862
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author Gonay, Leolo
Spourquet, Catherine
Baudoin, Matthieu
Lepers, Ludovic
Lemoine, Pascale
Fletcher, Alexander G.
Hanert, Emmanuel
Pierreux, Christophe E.
author_facet Gonay, Leolo
Spourquet, Catherine
Baudoin, Matthieu
Lepers, Ludovic
Lemoine, Pascale
Fletcher, Alexander G.
Hanert, Emmanuel
Pierreux, Christophe E.
author_sort Gonay, Leolo
collection PubMed
description Organogenesis is the phase of embryonic development leading to the formation of fully functional organs. In the case of the thyroid, organogenesis starts from the endoderm and generates a multitude of closely packed independent spherical follicular units surrounded by a dense network of capillaries. Follicular organisation is unique and essential for thyroid function, i.e. thyroid hormone production. Previous in vivo studies showed that, besides their nutritive function, endothelial cells play a central role during thyroid gland morphogenesis. However, the precise mechanisms and biological parameters controlling the transformation of the multi-layered thyroid epithelial primordium into a multitude of single-layered follicles are mostly unknown. Animal studies used to improve understanding of organogenesis are costly and time-consuming, with recognised limitations. Here, we developed and used a 2-D vertex model of thyroid growth, angiogenesis and folliculogenesis, within the open-source Chaste framework. Our in silico model, based on in vivo images, correctly simulates the differential growth and proliferation of central and peripheral epithelial cells, as well as the morphogen-driven migration of endothelial cells, consistently with our experimental data. Our simulations further showed that reduced epithelial cell adhesion was critical to allow endothelial invasion and fission of the multi-layered epithelial mass. Finally, our model also allowed epithelial cell polarisation and follicular lumen formation by endothelial cell abundance and proximity. Our study illustrates how constant discussion between theoretical and experimental approaches can help us to better understand the roles of cellular movement, adhesion and polarisation during thyroid embryonic development. We anticipate that the use of in silico models like the one we describe can push forward the fields of developmental biology and regenerative medicine.
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spelling pubmed-82163952021-06-22 Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches Gonay, Leolo Spourquet, Catherine Baudoin, Matthieu Lepers, Ludovic Lemoine, Pascale Fletcher, Alexander G. Hanert, Emmanuel Pierreux, Christophe E. Front Endocrinol (Lausanne) Endocrinology Organogenesis is the phase of embryonic development leading to the formation of fully functional organs. In the case of the thyroid, organogenesis starts from the endoderm and generates a multitude of closely packed independent spherical follicular units surrounded by a dense network of capillaries. Follicular organisation is unique and essential for thyroid function, i.e. thyroid hormone production. Previous in vivo studies showed that, besides their nutritive function, endothelial cells play a central role during thyroid gland morphogenesis. However, the precise mechanisms and biological parameters controlling the transformation of the multi-layered thyroid epithelial primordium into a multitude of single-layered follicles are mostly unknown. Animal studies used to improve understanding of organogenesis are costly and time-consuming, with recognised limitations. Here, we developed and used a 2-D vertex model of thyroid growth, angiogenesis and folliculogenesis, within the open-source Chaste framework. Our in silico model, based on in vivo images, correctly simulates the differential growth and proliferation of central and peripheral epithelial cells, as well as the morphogen-driven migration of endothelial cells, consistently with our experimental data. Our simulations further showed that reduced epithelial cell adhesion was critical to allow endothelial invasion and fission of the multi-layered epithelial mass. Finally, our model also allowed epithelial cell polarisation and follicular lumen formation by endothelial cell abundance and proximity. Our study illustrates how constant discussion between theoretical and experimental approaches can help us to better understand the roles of cellular movement, adhesion and polarisation during thyroid embryonic development. We anticipate that the use of in silico models like the one we describe can push forward the fields of developmental biology and regenerative medicine. Frontiers Media S.A. 2021-06-07 /pmc/articles/PMC8216395/ /pubmed/34163435 http://dx.doi.org/10.3389/fendo.2021.655862 Text en Copyright © 2021 Gonay, Spourquet, Baudoin, Lepers, Lemoine, Fletcher, Hanert and Pierreux https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Gonay, Leolo
Spourquet, Catherine
Baudoin, Matthieu
Lepers, Ludovic
Lemoine, Pascale
Fletcher, Alexander G.
Hanert, Emmanuel
Pierreux, Christophe E.
Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches
title Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches
title_full Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches
title_fullStr Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches
title_full_unstemmed Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches
title_short Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches
title_sort modelling of epithelial growth, fission and lumen formation during embryonic thyroid development: a combination of computational and experimental approaches
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216395/
https://www.ncbi.nlm.nih.gov/pubmed/34163435
http://dx.doi.org/10.3389/fendo.2021.655862
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