HOXB-5 EXPRESSION IN THE DEVELOPING MOUSE LUNG SUGGESTS A ROLE IN BRANCHING MORPHOGENESIS AND EPITHELIAL-CELL FATE

Hoxb-5 is one of the few homeobox genes strongly expressed in the deve loping mouse lung. To explore the hypothesis that Hoxb-5 acts to regul ate epithelial cell fate and branching morphogenesis in the developing lung, we Studied the temporal, spatial, and cell-specific expression of Hoxb-5 from gestational day (d) 13.5 to postnatal day (P) 2. Immuno cytochemistry demonstrated regional localization of Hoxb-5 protein to developing conducting airways and surrounding mesenchyme. The cellular expression pattern changed from diffusely positive nuclei of mesenchy mal cells on d13.5 to become more localized to nuclei of subepithelial fibroblasts and some adjacent columnar and cuboidal epithelial cells on d14.5. After d14.5, Hoxb-5 protein expression continued to decrease in mesenchymal cells distal from developing airways, but persisted in fibroblasts underlying conducting airways. Hoxb-5 protein expression persisted in nuclei of columnar and cuboidal epithelial cells on d16.5 and d17.5, with expression in low cuboidal epithelial cells as well f rom d17.5 to P2. Western blot analysis showed temporal and quantitativ e changes in Hoxb-5 protein expression with peak expression on d14.5-1 5.5. We conclude that Hoxb-5 protein is developmentally regulated in a temporal, spatial, and cell-specific manner throughout the pseudoglan dular, canalicular, and terminal saccular periods of lung development in the mouse. This localization and expression pattern suggests that H oxb-5 may influence branching morphogenesis, cell-cell communication, cell fate, and differentiation of conducting airway epithelia.