EXPRESSION OF HOXB GENES IN THE DEVELOPING MOUSE FOREGUT AND LUNG

Lung development in the mouse begins at embryonic day 9.5 (E9.5) when lung buds form in the foregut. Subsequently, there is extensive branch ing and cellular differentiation that depends upon specific epithelial -mesenchymal interactions. Homeobox genes are expressed in specific t emporo-spatial patterns in the developing embryo and are known to be i nvolved in axial patterning and specification of regional identity. Us ing whole mount in situ hybridization and immunohistochemistry, we stu died the expression of Hoxb-1, b-2, b-3, b-4 and b-5 in the E9.5-E14.5 foreguts and lungs. Our results show that in E9.5 branchial arches an d foregut, Herb genes are expressed in overlapping spatial domains and the anterior boundaries of these domains correspond to the position o f a particular gene in the cluster-genes on the 3' end of the cluster are expressed more anteriorly in the branchial arches and foregut and those on the 5' end are expressed more posteriorly. Three of the genes , Hoxb-3, b-4, and b-5, are highly expressed in the foregut where the lung buds form. In contrast, in E10.5-E14.5 lung, there are two patter ns of Herb gene expression. Hoxb-3 and b-4 are expressed in the mesenc hyme of the trachea, mainstem bronchi, and distal lung, whereas Hoxb-2 and b-5 mRNA are present only in the mesenchyme of the distal lung bu ds. These results suggest that specific combinations of Herb gene expr ession are important in lung development and that Herb genes may be in volved in specifying the differences between proximal (trachea and mai n bronchi) and distal (lung bud) mesenchyme.