THYROID TRANSCRIPTION FACTOR-I, HEPATOCYTE NUCLEAR FACTOR-3-BETA, SURFACTANT PROTEIN-B, PROTEIN-C, AND CLARA CELL SECRETORY PROTEIN IN DEVELOPING MOUSE LUNG

We used immunohistochemical analysis to localize thyroid transcription factor-1 (TTF-1), hepatocyte nuclear factor-3 beta (HNP-3 beta), pros urfactant proteins B and C (pro-SPB, pro-SP-C), surfactant protein B ( SP-B), and Clara cell secretory protein (CCSP) in developing mouse lun g. TTF-1 and HNF-3 beta were expressed at the onset of lung morphogene sis (gestational Day 10) and throughout fetal lung development, being detected in the nuclei of airway epithelial cells. TTF-1 was most prom inent in distal airway epithelial cells in embryonic lung and HNF-3B i n proximal bronchial and bronchiolar epithelial cells. Pro-SP-B and pr o-SP-C were first detected on gestational Day 11, being localized to t he cytoplasm of airway epithelial cells. Expression of both pro-protei ns was confined to distal airway epithelial cells from gestational Day 12 to Day 16. From gestational Day 17 and thereafter, pro-SP-B was de tectable in Type II cells and bronchiolar epithelial cells, whereas pr o-SP-C was restricted to Type II cells. SP-B peptide was first detecte d on gestational Day 17 in the cytoplasm of Type II cells and within t he lumen of distal airways. SP-B peptide was detectable only in the cy toplasm of Type II cells in adult lung. CCSP was first detected on ges tational Day 17, being localized to the cytoplasm of columnar epitheli al cells lining the conducting airways. Pro-SP-B, SP-B, pro-SP-C, and CCSP staining increased before birth. The early expression of TTF-1 an d HNF-3 beta, preceding and overlapping that of pro-SP-B, mature SP-B, pro-SP-C, and CCSP, supports a regulatory role for TTF-1 and HNF-3 be ta in lung-specific gene expression.