Thyroid C cells (or parafollicular cells) are neuroendocrine cells found in the thyroid gland that secrete calcitonin. To date, it has been thought that these cells arise from the neural crest but here, on p. , Mikael Nilsson and co-workers overturn this view. Using lineage tracing, they show that Wnt1-positive neural crest cells do not give rise to C cells in the mouse embryonic thyroid gland. Instead, they reveal, thyroid C cells are derived from Sox17-positive anterior endoderm. The researchers further show that the transcription factors Foxa1 and Foxa2, which are known to play a role in the development of other endoderm-derived populations, are co-expressed in C cell precursors, where they play non-redundant roles. Finally, the authors also show that Foxa1 and Foxa2 are expressed and appear to play distinct roles in human medullary thyroid carcinoma (MTC) cells. Together, these findings disprove the current concept of a neural crest origin of thyroid C cells and argue that MTC tumours should be reclassified as neuroendocrine tumours with an endodermal origin, a change that, from a clinical perspective, may open up new avenues in the search for MTC treatments.
