Opitz, R., Maquet, E., Zoenen, M., Dadhich, R., and Costagliola, S. (2011) TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish. Molecular endocrinology (Baltimore, Md.). 25(9):1579-99.
TSH is the primary physiological regulator of thyroid gland function. The effects of TSH on thyroid cells are mediated via
activation of its membrane receptor [TSH receptor (TSHR)]. In this study, we examined functional thyroid differentiation in
zebrafish and characterized the role of TSHR signaling during thyroid organogenesis. Cloning of a cDNA encoding zebrafish
Tshr showed conservation of primary structure and functional properties between zebrafish and mammalian TSHR. In situ hybridization confirmed that the thyroid is the major site of tshr expression during zebrafish development. In addition, we identified tpo, iyd, duox, and duoxa as novel thyroid differentiation markers in zebrafish. Temporal analyses of differentiation marker expression demonstrated
the induction of an early thyroid differentiation program along with thyroid budding, followed by a delayed onset of duox and duoxa expression coincident with thyroid hormone synthesis. Furthermore, comparative analyses in mouse and zebrafish revealed for
the first time a thyroid-enriched expression of cell death regulators of the B-cell lymphoma 2 family during early thyroid
morphogenesis. Knockdown of tshr function by morpholino microinjection into embryos did not affect early thyroid morphogenesis but caused defects in later
functional differentiation. The thyroid phenotype observed in tshr morphants at later stages comprised a reduction in number and size of functional follicles, down-regulation of differentiation
markers, as well as reduced thyroid transcription factor expression. A comparison of our results with phenotypes observed
in mouse models of defective TSHR and cAMP signaling highlights the value of zebrafish as a model to enhance the understanding
of functional differentiation in the vertebrate thyroid.