Institute for Developmental Biology, University of Cologne


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Dr. Klaus B. Rohr

Molecular and cellular aspects of thyroid development

The thyroid gland develops from the ventral midline of the pharynx. After evagination from the pharyngeal epithelium, the thyroid primordium relocates deep into the cervical mesenchyme, in humans finally reaching a position at the base of the neck, in front of the trachea (Figure 1). In humans, defects in thyroid development can cause absence of the thyroid gland at birth (agenesis) or malformations like ectopic localisation of the gland. Such defects can compromise thyroid hormone production and then lead to congenital hypothyroidism. The molecular, genetic and cellular basis of thyroid development is poorly understood. A few genes have been identified to be required for thyroid development, most of them encoding transcription factors that are required in primordial cells for differentiation and, at least in part, for later thyroid hormone production. However, it is still unknown how the thyroid primordium is induced, what the molecular mechanisms of relocation ("migration") are and how the gland is morphogenetically shaped.

In our current projects, we analyse various aspects of thyroid development mainly in zebrafish, and to a lesser extend also in mouse and lamprey. Our goal is to understand how the gland develops on the cellular and molecular level. Identification and characterisation of zebrafish mutants allow us to identify so far unknown genes required for thyroid development (Figure 2). Zebrafish embryos are particularly well suited for analyses and embryonic manipulation due to their transparency, rapid development, and large clutches of eggs. Morphologically, the zebrafish thyroid develops basically like in other vertebrates. A minor difference is that fish do not form a compact gland, but have their thyroid tissue dispersed along the ventral aorta (anatomically this is very similar to the position of the gland in mammals, Figure 3). Molecular mechanisms are conserved: we found that the genes Thyroid Transcription Factor1, Pax8, and Hhex have comparable functions in zebrafish and mouse thyroid development. The lamprey is of particular interest, because here an ancestral larval precursor organ, the endostyle, transforms into the adult thyroid during metamorphosis. Thus, in lampreys, ontogeny recapitulates the evolution of the thyroid gland, a process that we try to understand on the molecular level.

Our work was funded as a Junior Group in the SFB 572 “Committment of Cell Arrays and Cell Type Specification" at the University of Cologne.

Publication list (search Pubmed for: Rohr-KB).




	Figure 1: Position of the thyroid gland in humans.




	Figure 2: Zebrafish embryos, after in situ hybridisation with nk2.1a, a marker for the thyroid primordium that also labels parts of the brain. In a mutant, only the brain expression is visible, because the thyroid is missing. Such mutants serve as models to understand congenital hypothyroidism.




	Figure 3: Concomitant with the separation of systemic and pulmonary circulation, the mammalian aortic arch and corresponding side vessels (right) evolved from an ancestral symmetric circulatory system as it is still present in fish (left). Note the distribution of thyroid tissue (green).