Shaping the thyroid: From peninsula to de novo lumen formation

https://doi.org/10.1016/j.mce.2021.111313Get rights and content

Highlights

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    Thyroid development starts by formation of a mass of unpolarized epithelial cells.

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    The thyroid mass fragments into a multitude of independent spherical follicles.

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    Follicles are composed of polarized epithelial cells facing the colloid and surrounded by blood vessels.

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    Follicle formation occurs by de novo lumen formation and induced mirror polarization.

Abstract

A challenging and stimulating question in biology deals with the formation of organs from groups of undifferentiated progenitor cells. Most epithelial organs indeed derive from the endodermal monolayer and evolve into various shape and tridimensional organization adapted to their specialized adult function. Thyroid organogenesis is no exception. In most mammals, it follows a complex and sequential process initiated from the endoderm and leading to the development of a multitude of independent closed spheres equipped and optimized for the synthesis, storage and production of thyroid hormones. The first sign of thyroid organogenesis is visible as a thickening of the anterior foregut endoderm. This group of thyroid progenitors then buds and detaches from the foregut to migrate caudally and then laterally. Upon reaching their final destination in the upper neck region on both sides of the trachea, thyroid progenitors mix with C cell progenitors and finally organize into hormone-producing thyroid follicles. Intrinsic and extrinsic factors controlling thyroid organogenesis have been identified in several species, but the fundamental cellular processes are not sufficiently considered. This review focuses on the cellular aspects of the key morphogenetic steps during thyroid organogenesis and highlights similarities and common mechanisms with developmental steps elucidated in other endoderm-derived organs, despite different final architecture and functions.

Section snippets

The thyroid gland

In most mammals, the thyroid gland is an endocrine bilobed gland located in the neck region, in front of the trachea and close to the thyroid cartilage. Its parenchyma is constituted of a multitude of independent spherical units, the follicles. Each follicle is formed by a monolayer of epithelial cells, the follicular cells or thyrocytes, surrounding a lumen filled with a proteinaceous substance, the colloid. Follicular cells in this particular organization synthesize and release the thyroid

Endoderm and primitive gut tube

Early in vertebrate development, gastrulation results in the formation of three germ layers: (i) the ectoderm, which will generate the skin and the central nervous system, (ii) the mesoderm, which will form the blood, the bones, and the muscles, and (iii) the endoderm, which will contribute to the respiratory and gastrointestinal tracts and the associated organs or glands. After gastrulation, the endoderm consists of a monolayer of polarized epithelial cells separating the mesoderm on their

Migration of the midline thyroid primordium

Thyroid bud progressively elongates caudally with the cranial extremity still connected to the pharyngeal endoderm by a thin thread of cells, the thyroglossal duct. The caudal extremity of the bud becomes separated from the wall of the aortic sac by mesenchymal cells that undergo intense proliferation. Starting at E10.5, few proliferative (BrdU+) cells can now be detected in the descending thyroid primordium, indicating growth of the thyroid bud by cell proliferation during migration.

At around

Morphogenesis and folliculogenesis

Morphogenesis and folliculogenesis occur simultaneously with thyroid lobes enlargement and differentiation and are inseparable processes. The role of proliferation in the expansion of small peripheral buds or cords of cells was discussed (see under 3). Non-exclusive hypotheses explaining why and how only some groups of peripheral cells undergo outward growth were also presented. With respect to folliculogenesis or the formation of the angio-follicular units, the perfusion-independent role of

Concluding remarks and future directions

A number of studies in various animal models have described the morphological steps of thyroid organogenesis and have identified intrinsic and extrinsic molecular actors or factors involved directly or indirectly in thyroid development. However, the cellular mechanisms at play during budding, migration, bilobation, morphogenesis and folliculogenesis remain poorly understood. Here, I summarized thyroid developmental steps and using an integrative view with other endoderm-derived organ

Acknowledgements

Past and present members of the CELL unit are acknowledged for valuable input in data collection and discussions, and in particular Catherine Spourquet and Léolo Gonay for Fig. 2 preparation. CEP wants to thank his daughters for their unwanted input in the “mirror polarization” concept. CEP is funded by UCLouvain (ARC 065-15/20), F.R.S.-FNRS and Fondation Roi Baudouin, and Pan3DP FET Open (EU Horizon 2020 research and innovation programme under grant agreement No 800981).

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