{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:29:22Z","timestamp":1787610562902,"version":"build-2736575974"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>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, <jats:italic>i.e.<\/jats:italic> thyroid hormone production. Previous <jats:italic>in vivo<\/jats:italic> 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 <jats:italic>in\u00a0silico<\/jats:italic> model, based on <jats:italic>in vivo<\/jats:italic> 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 <jats:italic>in silico<\/jats:italic> models like the one we describe can push forward the fields of developmental biology and regenerative medicine.<\/jats:p>","DOI":"10.3389\/fendo.2021.655862","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T16:21:38Z","timestamp":1623082898000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Modelling of Epithelial Growth, Fission and Lumen Formation During Embryonic Thyroid Development: A Combination of Computational and Experimental Approaches"],"prefix":"10.3389","volume":"12","author":[{"given":"Leolo","family":"Gonay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Spourquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Baudoin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Lepers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Lemoine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Hanert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe E.","family":"Pierreux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"B1","article-title":"Chapter 2 Thyroid Hormone Synthesis and Secretion","volume-title":"Endotext","author":"Rousset","year":"2000"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012-1015","article-title":"Recent Insights Into the Cell Biology of Thyroid Angiofollicular Units","volume":"34","author":"Colin","year":"2013","journal-title":"Endocr Rev"},{"key":"B3","article-title":"Ontogeny, Anatomy, Metabolism and Physiology of the Thyroid","volume-title":"Endotext","author":"Maenhaut","year":"2015"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0028","article-title":"Thyroid Development and Its Disorders: Genetics and Molecular Mechanisms","volume":"25","author":"De Felice","year":"2004","journal-title":"Endocr Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1242\/dev.145615","article-title":"Development of the Thyroid Gland","volume":"144","author":"Nilsson","year":"2017","journal-title":"Development"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20653","article-title":"The Developing Mouse Thyroid: Embryonic Vessel Contacts and Parenchymal Growth Pattern During Specification, Budding, Migration, and Lobulation","volume":"235","author":"Fagman","year":"2006","journal-title":"Dev Dyn"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4161\/org.4.4.7414","article-title":"VEGF and Endothelial Guidance in Angiogenic Sprouting","volume":"4","author":"Gerhardt","year":"2008","journal-title":"Organogenesis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2012.11.008","article-title":"Robustness in Angiogenesis: Notch and BMP Shaping Waves","volume":"29","author":"Beets","year":"2013","journal-title":"Trends Genet TIG"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.04.022","article-title":"Reciprocal Epithelial: Endothelial Paracrine Interactions During Thyroid Development Govern Follicular Organization and C-cells Differentiation","volume":"381","author":"Hick","year":"2013","journal-title":"Dev Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1242\/dev.134171","article-title":"Thyroid Follicle Development Requires Smad1\/5- and Endothelial Cell-Dependent Basement Membrane Assembly","volume":"143","author":"Villacorte","year":"2016","journal-title":"Dev Camb Engl"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2098","article-title":"Biology by Numbers: Mathematical Modelling in Developmental Biology","volume":"8","author":"Tomlin","year":"2007","journal-title":"Nat Rev Genet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.semcdb.2015.07.001","article-title":"How Computational Models can Help Unlock Biological Systems. 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