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Zusammenfassung:
The thyroid is an endocrine gland in all vertebrates that develops from the ventral floor of the anterior pharyngeal endoderm.
Unravelling the molecular mechanisms of thyroid development helps to understand congenital hypothyroidism caused by the
absence or reduction of this gland in newborn humans. Severely reduced or absent thyroid-specific developmental genes
concomitant with the complete loss of the functional gland in the zebrafish hands off (han, hand2) mutant reveals the han gene as
playing a novel, crucial role in thyroid development. han-expressing tissues surround the thyroid primordium throughout
development. Fate mapping reveals that, even before the onset of thyroid-specific developmental gene expression, thyroid
precursor cells are in close contact with han-expressing cardiac lateral plate mesoderm. Grafting experiments show that han is
required in surrounding tissue, and not in a cell-autonomous manner, for thyroid development. Loss of han expression in the
branchial arches and arch-associated cells after morpholino knock-down of upstream regulator genes does not impair thyroid
development, indicating that other han-expressing structures, most probably cardiac mesoderm, are responsible for the thyroid
defects in han mutants. The zebrafish ace (fgf8) mutant has similar thyroid defects as han mutants, and chemical suppression of
fibroblast growth factor (FGF) signalling confirms that this pathway is required for thyroid development. FGF-soaked beads can
restore thyroid development in han mutants, showing that FGFs act downstream of or in parallel to han. These data suggest that
loss of FGF-expressing tissue in han mutants is responsible for the thyroid defects.
