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pax2.1 is required for the development of thyroid follicles in zebrafish

Thomas Wendl¹, Klaus Lun², Marina Mione³, Jack Favor⁴, Michael Brand², Stephen W. Wilson³ and Klaus B. Rohr^3,*,

¹ Institute for Developmental Biology, University of Cologne, Gyrhofstrasse 17, D-50923 Köln, Germany
² Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany
³ Department of Anatomy and Developmental Biology, UCL, Gower Street, London WC1E 6BT, UK
⁴ GSF-National Research Center for Environment and Health, Institute for Human Genetics, Ingolstaedter Landstr. 1, D-85764 Neuherberg, Germany
^* Present address: Institute for Developmental Biology, University of Cologne, Gyrhofstrasse 17, D-50923 Köln, Germany

Author for correspondence (e-mail: klaus.rohr{at}uni-koeln.de)

Accepted 30 April 2002

The thyroid gland is an organ primarily composed of endoderm-derived follicular cells. Although disturbed embryonic development of the thyroid gland leads to congenital hypothyroidism in humans and mammals, the underlying principles of thyroid organogenesis are largely unknown. In this study, we introduce zebrafish as a model to investigate the molecular and genetic mechanisms that control thyroid development. Marker gene expression suggests that the molecular pathways of early thyroid development are essentially conserved between fish and mammals. However during larval stages, we find both conserved and divergent features of development compared with mammals. A major difference is that in fish, we find evidence for hormone production not only in thyroid follicular cells, but also in an anterior non-follicular group of cells.

We show that pax2.1 and pax8, members of the zebrafish pax2/5/8 paralogue group, are expressed in the thyroid primordium. Whereas in mice, only Pax8 has a function during thyroid development, analysis of the zebrafish pax2.1 mutant no isthmus (noi^–/–) demonstrates that pax2.1 has a role comparable with mouse Pax8 in differentiation of the thyroid follicular cells. Early steps of thyroid development are normal in noi^–/–, but later expression of molecular markers is lost and the formation of follicles fails. Interestingly, the anterior non-follicular site of thyroid hormone production is not affected in noi^–/–. Thus, in zebrafish, some remaining thyroid hormone synthesis takes place independent of the pathway leading to thyroid follicle formation. We suggest that the noi^–/– mutant serves as a new zebrafish model for hypothyroidism.

Key words: Hypothyroidism, Thyroid, Pax2, Pax8, Nkx2.1, TTF1, Evolution, Zebrafish, Mouse

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