Pax2.1 is required for the development of thyroid follicles in zebrafish.
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.
Wendl
Thomas
T
Institute for Developmental Biology, University of Cologne, Gyrhofstrasse 17, D-50923 Köln, Germany.
Lun
Klaus
K
Mione
Marina
M
Favor
Jack
J
Brand
Michael
M
Wilson
Stephen W
SW
Rohr
Klaus B
KB
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004625:Embryo, Nonmammalian; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics; D017403:In Situ Hybridization; D051379:Mice; D009154:Mutation; D051762:PAX2 Transcription Factor; D013961:Thyroid Gland / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D013974:Thyroxine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; C497319:Pax2 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C497320:pax2a protein, zebrafish; D013974:Thyroxine