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. 2021 Apr 20;12:666565. doi: 10.3389/fendo.2021.666565

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Copyright © 2021 Posabella, Alber, Undeutsch, Droeser, Hollenberg, Ikonomou and Kotton

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.

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Thyroid development overview. The thyroid morphogenesis in mice can be divided in 5 different steps: 1. Thyroid specification: occurs in the definitive endoderm-derived gut tube at embryonic day (E) 8.5 in mice and day post fertilization (DPF) 20-22 in human and is characterized by a thickening of a restricted area of the pharyngeal endoderm within the anterior ventral foregut epithelium, caudal to the first branchial branch, called the placode. The resulting foregut endoderm derived cells in the placode upregulate Nkx2-1 and Pax8, the earliest known gene markers of “thyroid specification,” and represent the small pool of endodermal primordial thyroid progenitors from which the entire adult thyroid follicular epithelium will derive. 2. Budding: a progressive increase in thickness of the placode determines an evagination of the pharyngeal endodermal tissue, firstly visible at day E9.5 in mice and DPF 24 in human. 3. Migration: at E10-10.5 in mice and DPF 26 in human, the thyroid primordium begins its migration to pretracheal position. At the moment of detachment, the thyroglossal duct degenerates, leaving the thyroid bud completely surrounded by mesenchymal tissue, losing any contact with the floor of the pharynx. 4. Bilobation: the earliest signs of the bilobation can be observed at E11.5 in mice, when the thyroid shape changes from spherical to oval but it is only at E12.5 in mice that the thyroid extends bilaterally along the third pharyngeal arch arteries reaching its definitive shape. In human the bilobation takes approximately 20 days, from DPF 28 until DPF 48. During this process the thyroid primordium fuses with paired ultimobranchial bodies (UBB), lateral anlagen originating from the fourth pharyngeal pouches, designated to a C-Cell (calcitonin-producing cell) fate. 5. Folliculogenesis: once the bilobation is complete, the thyroid undergoes folliculogenesis. During this process, from E14.5 to E17.5 in mouse and from DPF 60 to DPF 84 in human, thyroid follicular epithelial cells (thyrocytes) acquire epithelial polarity and the follicular lumen gradually grows, resulting into the final shape of the follicle. Vascularized, polarized follicles comprise the functional and morphological thyroid unit, namely the angio-follicular thyroid unit.