Endocrine Abstracts

Thyroid dysgenesis (comprising agenesis, hemiagenesis or ectopic localization) is the major cause of congenital hypothyroidism in humans. Recent experimental observations indicate that thyroid dysgenesis may be a polygenic disease with variable penetrance depending on genetic background. Also, thyroid dysgenesis might be one manifestation of syndromic malformations. The molecular mechanisms of thyroid dysgenesis in humans are largely unknown; so far genes encoding thyroid transcription factors that are required for normal thyroid development in mouse, i.e. Titf1/Nkx2.1 (also known as TTF-1), Foxe1 (also known as TTF-2) and Pax8, have been found to be mutated only in a minority of patients. The underlying molecular mechanism is in most cases unknown, but the frequent co-incidence of cardiac anomalies (3–12%) suggests that the thyroid morphogenetic process may be linked to cardiovascular development.

I will give an overview about critical steps in murine thyroid morphogenesis. Emphasis will be put on proliferative patterns and the possible relationship between shaping of the thyroid and development of the of pharyngeal arch artery system. In this context, recent results from our laboratory providing a mechanistic explanation to thyroid dysgenesis incidentally reported to occur in children with the DiGeorge syndrome will be discussed. The role of non-cell-autonomous factors (Shh, Tbx1) in thyroid development will be put in relation to other transgenic models where thyroid dysgenesis has been described. Finally, possible clinical implications of the findings will be discussed.