TTF-1, a homeodomain-containing transcription factor, which is required for the specific expression of the thyroglobulin and thyroperoxidase gene promoters in differentiated thyroid cell lines, is expressed at the very beginning of rat thyroid differentiation. TTF-1 mRNA is detected in the endodermal cells of the thyroid rudiment in the rat embryo and precedes the expression of the two known target genes by 5 days. No delay is observed between the appearance of TTF-1 mRNA and protein, which shows a clear nuclear localization. In the adult thyroid, TTF-1 is present only in the endoderm-derived follicular cells. Two additional domains of expression of TTF-1 have been observed, the lung and restricted areas of the brain. In the lung, TTF-1 mRNA and protein are also present at the earliest stages of differentiation and are later confined to the bronchial epithelium. In the brain, TTF-1 appears to be restricted to structures of diencephalic origin, including the developing neurohypophysis. The early detection of TTF-1 in the endodermal cells of the thyroid and lung anlage and in restricted neuroblast populations indicates that TTF-1 may have a role in cell determination in these three systems and that additional mechanisms may be involved in the activation of thyroid-specific gene expression.

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