An in vivo study of signaling pathways involved in zebrafish thyroid formation.

The molecular pathways contributing to thyroid development and function appear to be highly conserved in vertebrates; similar to mammals, the zebrafish thyroid gland is composed of endoderm-derived follicles, filled with colloid and producing thyroid hormones. However, the precise role of different pathways in the several morphogenetic steps, occurring during thyroid development, and their activity in the surrounding tissues remain to be clarified. A better comprehension of these mechanisms is expected to offer novel working hypothesis on the molecular and genetic basis of human thyroid dysgenesis. In our study we aim to characterize and systematically dissect the role of key signaling pathways, throughout the main steps of zebrafish thyroid formation. To this purpose, we are taking advantage of a series of zebrafish signaling pathway reporter lines, maintained or specifically generated by our group. In particular, we are focusing our attention on the following signaling cascades: Bmp, Shh, Fgf, Wnt, Notch, cAMP, Hypoxia, Stat3, Glucocorticoid. These transgenic lines, expressing green (GFP) or red (mCherry) fluorescent proteins in response to specific signaling activation, are currently in vivo monitored from the early steps of thyroid primordium induction and budding until the final stages of migration, follicular polarization and hormone production. Relevant pathways, activated nearby or within the thyroid region, will be subjected to further validation using pathway-specific agonists/antagonists or mutant/morphant conditions, in order to precisely dissect the role of a given signal on thyroid formation and function. Preliminary results of this study will be presented and discussed.