**2.1. Embryological development of the thyroid gland and origin of C cells**

The thyroid gland has a dual embryonic origin. Most of the thyroid gland derives from the medial anlage, a ventral outpocketing of the foregut endoderm at the level of the first pair of pharyngeal pouches. The medial anlage appears as a bilobulate vesicular structure at the foramen caecum of the tongue. It then descends as a component of the thyroglosal duct to reach its definitive position in the neck. After involution of the thyroglosal duct, the thyroid anlage begins to expand laterally to form two lateral lobes and a medial isthmus between them. Consequently, the medial anlage gives rise to most, if not all, of the follicular epithelium [3].

On the other hand, C cells derive from the ultimobranchial bodies (UBB), two outpocketings of the forth-fifth pharyngeal pouch complexes that lose their connection and migrate centrally to fuse with the medial thyroid anlage. Fusion typically occurs slightly above to the middle of the lateral lobes. After incorporation into the larger medial anlage, cells of the UBB disperse into the surrounding thyroid tissue and give rise to C cells. UBB may also contribute to the formation of a minimal part of thyroid follicular cells [4]. Finally, portions of the UBB persist in the postnatal thyroid glands as small cystic structures -the "**ultimobranchial follicles**"- in rodents [5], or as "**solid cell nests**" in humans [6]. Estimates of the relative contributions to thyroid weight from the lateral anlage range from less than 1 to 30% in humans [7]. In non-mammal vertebrates, the embryonic thyroid and UBB develop as separate structures, thus, C cells are confined to the ultimobranchial glands derived from the UBB, where they secrete calcitonin [8].

Since Le Douarin and Le Lievre study [9] confirmed, using chick-quail chimeras, that avian ultimobranchial C cells originate from the neural crests, it was assumed, without much supporting evidence, that mammalian thyroid C cells also originate from the neural crest via the UBB. Nevertheless, the neuroectodermical origin of C cells in mammals is currently a controversial subject. In fact, Kameda et al. [10] have recently presented evidence that murine C cells are derived from the endodermal epithelial cells of the last pharyngeal pouch -UBB- and do not originate from neural crest cells.
