Thyroid transcription factor-1, hepatocyte nuclear factor-3beta, surfactant protein B, C, and Clara cell secretory protein in developing mouse lung.

Abstract

We used immunohistochemical analysis to localize thyroid transcription factor-1 (TTF-1), hepatocyte nuclear factor-3beta (HNF-3beta), prosurfactant proteins B and C (pro-SP-B, pro-SP-C), surfactant protein B (SP-B), and Clara cell secretory protein (CCSP) in developing mouse lung. TTF-1 and HNF-3beta were expressed at the onset of lung morphogenesis (gestational Day 10) and throughout fetal lung development, being detected in the nuclei of airway epithelial cells. TTF-1 was most prominent in distal airway epithelial cells in embryonic lung and HNF-3beta in proximal bronchial and bronchiolar epithelial cells. Pro-SP-B and pro-SP-C were first detected on gestational Day 11, being localized to the cytoplasm of airway epithelial cells. Expression of both pro-proteins was confined to distal airway epithelial cells from gestational Day 12 to Day 16. From gestational Day 17 and thereafter, pro- SP-B was detectable in Type II cells and bronchiolar epithelial cells, whereas pro-SP-C was restricted to Type II cells. SP-B peptide was first detected on gestational Day 17 in the cytoplasm of Type II cells and within the lumen of distal airways. SP-B peptide was detectable only in the cytoplasm of Type II cells in adult lung. CCSP was first detected on gestational Day 17, being localized to the cytoplasm of columnar epithelial cells lining the conducting airways. Pro-SP-B, SF-B, pro-SP-C, and CCSP staining increased before birth. The early expression of TTF-1 and HNF-3beta, 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-3beta in lung-specific gene expression.