TEMPORAL-SPATIAL DISTRIBUTION OF HEPATOCYTE NUCLEAR FACTOR-3-BETA IN DEVELOPING HUMAN LUNG AND OTHER FOREGUT DERIVATIVES

We assessed the temporal-spatial distribution of hepatocyte nuclear fa ctor-3 beta (HNF-3 beta) in developing human lung and other foregut de rivatives. Tissue from 31 fetuses (10-40 weeks) and 24 infants with hy aline membrane disease (HMD) or bronchopulmonary dysplasia (BPD) (2 da ys to 7 months) was studied. HNF-3 beta was detected in nuclei of epit helial cells of trachea and of conducting and terminal airways at 10 w eeks. Thereafter, epithelial nuclei were immunolabeled more widely in peripheral than proximal airways. HNF-3 beta was confined to bronchiol o-alveolar portals and Type II cells in nonfetal lung. In infants with BPD, HNF-3 beta was expressed abundantly in regenerating epithelial c ells at the periphery of lung lobules. HNF-3 beta was also detected in fetal esophagus, pancreas, duodenum, stomach, and gallbladder, sugges ting that it is a marker for progenitor cells in foregut derivatives. The pattern of expression of HNF-3 beta in the lung was similar to tha t of thyroid transcription factor-1 (TTF-1) at all ages. The temporal- spatial patterns of HNF-3 beta and TTF-1 in the developing and regener ating lung are consistent with their proposed role in epithelial cell differentiation, regeneration, and surfactant protein gene expression.