Developmental mucin gene expression in the human respiratory tract

The epithelial surface of the respiratory tract is coated with a protective film of mucus secreted by epithelial goblet and submucosal gland cells. Hi stology of the airway mucosa and composition of secretions during the secon d trimester of fetal life are known to differ from the normal adult in that these secretions show similarities with those of hypersecretory disorders. To provide information regarding cell-specific expression of mucin genes a nd their relation to developmental patterns of epithelial cytodifferentiati on, we studied the expression of eight different mucin genes (MUC1-MUC4, MU C5AC, MUC5B, MUC6, MUC7) in human embryonic and fetal respiratory tract usi ng in situ hybridization. These investigations demonstrated that MUC4 is th e earliest gene expressed in the foregut at 6.5 wk, followed by MUC1 and MU C2 from 9.5 wk of gestation in trachea, bronchi, epithelial tubules, and te rminal sacs before epithelial cytodifferentiation. In contrast, MUC5AC, MUC 5B, and MUC7 are expressed at later gestational ages concomitant with epith elial cytodifferentiation. During this developmental stage, MUC1 and MUC4 m RNAs are located in goblet and ciliated cells, whereas MUC2 mRNAs are locat ed in basal and goblet cells. MUC5AC expression is confined to goblet cells . In the submucosal glands, MUC2 mRNAs are located in both mucous and serou s cells, whereas MUC5B and MUC7 mRNAs are expressed in mucous and in serous cells, respectively. These data suggest distinct developmental roles far M UC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7 in the elongation, branching, and epithelial cytodifferentiation of the respiratory tract during ontogenesis. Distinct patterns of mucin gene expression are also likely to play an impo rtant role in regulating appropriate epithelial cell proliferation and cyto differentiation in adult airway mucosa as it is indicated by aberrant expre ssion in hypersecretory disorders.