Mesodermal FGF and BMP govern the sequential stages of zebrafish thyroid specification

Thyroid tissue, the site of de novo thyroid hormone biosynthesis, is derived from ventral pharyngeal endoderm and defects in morphogenesis are a predominant cause of congenital thyroid diseases. The first molecularly recognizable step of thyroid development is the specification of thyroid precursors in anterior foregut endoderm. Recent studies have identified crucial roles of FGF and BMP signaling in thyroid specification, but the interplay between signaling cues and thyroid transcription factors remained elusive. By analyzing Pax2a and Nkx2.4b expression dynamics in relation to endodermal FGF and BMP signaling activities in zebrafish embryos, we identified a Pax2a-expressing thyroid progenitor population that shows enhanced FGF signaling but lacks Nkx2.4b expression and BMP signaling. Concurrent with upregulated BMP signaling, a subpopulation of these progenitors subsequently differentiates into lineage-committed thyroid precursors co-expressing Pax2a and Nkx2.4b. Timed manipulation of FGF/BMP activities suggests a model in which FGF signaling primarily regulates Pax2a expression, whereas BMP signaling regulates both Pax2a and Nkx2.4b expression. Our observation of similar expression dynamics of Pax8 and Nkx2-1 in mouse embryos suggests that this refined model of thyroid cell specification is evolutionarily conserved in mammals.

Automated summary

Thyroid tissue is derived from ventral pharyngeal endoderm and defects in morphogenesis are a main cause of congenital thyroid diseases. Recent studies have revealed the importance of FGF and BMP signaling in thyroid specification, but the relationship between signaling cues and thyroid transcription factors is still unclear. By analyzing zebrafish embryos, researchers identified a population of Pax2a-expressing thyroid progenitor cells that show enhanced FGF signaling but lack Nkx2.4b expression and BMP signaling. Manipulation of FGF/BMP activities suggests that FGF signaling mainly regulates Pax2a expression, while BMP signaling regulates both Pax2a and Nkx2.4b expression. Similar expression dynamics were observed in mouse embryos, indicating that this refined model of thyroid cell specification is evolutionarily conserved in mammals.