TTF-2, A NEW FORKHEAD PROTEIN, SHOWS A TEMPORAL EXPRESSION IN THE DEVELOPING THYROID WHICH IS CONSISTENT WITH A ROLE IN CONTROLLING THE ONSET OF DIFFERENTIATION

Expression of thyroglobulin (Tg) and thyroperoxidase (TPO) genes in th yroid follicular cells occurs in the mouse at embryonic day (E)14.5. T wo transcription factors, TTF-1 and Pax-8, have been implicated in tra nscriptional activation of Tg and TPO, even though the onset of their expression is at E9.5, suggesting that additional events are necessary for transcriptional activation of Tg and TPO genes. We report in this paper the cloning of TTF-2, a DNA binding protein that recognizes sit es on both Tg and TPO promoters, TTF-2 is a new forkhead domain-contai ning protein whose expression is restricted to the endodermal lining o f the foregut and to the ectoderm that will give rise to the anterior pituitary. TTF-2 shows transient expression in the developing thyroid and anterior pituitary. In the thyroid, TTF-2 expression is downregula ted just before the onset of Tg and TPO gene expression, suggesting th at this transcription factor plays the role in development of a negati ve controller of thyroid-specific gene expression.