Sabine Costagliola Lab

The Thyroid gland

Thyroid hormones are a class of iodide-containing molecules that play a critical role in the regulation of various body function including growth, metabolism and heart function and that are crucial for normal brain development. The thyroid gland, an endocrine organ that has been specialized in trapping iodide, is the only organ where these hormones are produced. It is, however, of note that one out of 3000 human newborns is born with congenital hypothyroidism (CHTD), a condition characterized by insufficient production of thyroid hormones. In the absence of a medical treatment with thyroid hormones initiated during the first days after birth - the child will be affected by an irreversible mental retardation. Moreover, a life-long hormonal treatment is necessary in order to maintain proper regulation of growth and general metabolism.

Thyroid development

Thyroid development is a complex process involving various morphogenetic events. Early after precursor cell specification in ventral foregut endoderm, primitive thyroid cells already have a distinct molecular signature, characterized by co-expression of four transcription factors; HHEX, NKX2.1, PAX8 and FOXE1. Thereafter, thyroid budding occurs, followed by migration of the primordium to a position distant from its site of origin and formation of functional thyroid follicles that express thyroid specific genes (e.g. Tg, TSHr, TPO, NIS) and produce thyroid hormones.

Congenital hypothyroidism

The majority of CHTD (85%) are due to thyroid dysgenesis, including athyreosis, hypoplasia, hemiagenesis or thyroid ectopy. These phenotypes are considered to be caused by defects during embryonic development. The molecular mechanisms underlying CHTD remain poorly understood. CHTD is predominantly non-syndromic and sporadic (i.e. 98% of cases are non-familial). Germinal mutations in thyroid related transcription factors NKX2.1, FOXE1, PAX-8, and NKX2.5 have been identified in only 3% of patients with sporadic CHTD. This indicates that other still unknown factors might play important roles during thyroid organogenesis.

Thyroid cancers

Thyroid cancers are the most frequent endocrine malignancies. They represent 1% of the total cancer burden in the Western world. Recent genome-wide association studies have uncovered single nucleotide polymorphism (SNP) associated with an increased risk of papillary thyroid cancer (PTC)—this histology represent 80% of all thyroid cancers and affects follicular cells—and thyroid function. The two SNPs most significantly associated with PTC risk discovered so far are located in the vicinity of FOXE1 (rs965513) and NKX2.1 (rs944289), suggesting that some differentiation defects promote PTCs.


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