The mammalian thyroid gland stands out in comparison to other organs as it develops from no less than three independent anlagen that originate in anterior endoderm. The median or central anlage present in the pharyngeal floor gives rise to the thyroid bud or diverticulum that provides progenitors to the thyroxin-producing follicular cells. Bilaterally, the ultimobranchial bodies bud off from the inferior-most pharyngeal pouch. Until recently those structures were considered merely as vehicles that brought neuroendocrine C cells of neural crest origin to the embryonic thyroid; by genetic lineage tracing in mice this concept is now abandoned in favour of an endoderm origin of thyroid C cell precursors, thus indicting that both endocrine cell lineages of the thyroid are foregut derivatives. Defective development of the midline primordium produces a spectrum of anatomical malformations collectively referred to thyroid dysgenesis, the most common cause of congenital hypothyroidism in humans. Only few of those patients have a mutation in today known thyroid developmental genes. The presentation will summarize the roles of established and newly discovered genes in thyroid morphogenesis before the pituitary gets control of the embryonic thyroid. A new concept of thyroid growth reminiscent of branching in e.g. lung development will be introduced. Deficient C cell development has no clinical phenotype, but transcription factors implicated in embryonic growth and migration of C cell precursors from endoderm may shed new light on the pathogenesis of medullary thyroid carcinoma in children with MEN2B, which will be discussed. Finally, in view of the possibility that the first somatic mutation in childhood papillary thyroid cancer may arise already in the foetus or infant, recent progress in tracing oncogenically mutant cells with a fluorescent transgene, with the purpose to investigate directly in the microscope putative interactions with bystander normal follicular cells before tumorigenesis gets started, will be presented.
10 Sep 2016 - 12 Sep 2016