Am. J. Respir. Cell Mol. Biol., Vol 15, No. 2, 08 1996, 163-171.
Expression of Hoxb genes in the developing mouse foregut and lung
CW Bogue, LJ Lou, H Vasavada, CM Wilson and HC Jacobs
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
Lung development in the mouse begins at embryonic day 9.5 (E9.5) when lung
buds form in the foregut. Subsequently, there is extensive branching and
cellular differentiation that depends upon specific epithelial-mesenchymal
interactions. Homeobox genes are expressed in specific temporo-spatial
patterns in the developing embryo and are known to be involved in axial
patterning and specification of regional identity. Using whole mount in
situ hybridization and immunohistochemistry, we studied 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 and foregut, Hoxb genes are
expressed in overlapping spatial domains and the anterior boundaries of
these domains correspond to the position of 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 patterns of Hoxb gene expression. Hoxb- 3
and b-4 are expressed in the mesenchyme 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 buds. These results suggest that specific
combinations of Hoxb gene expression are important in lung development and
that Hoxb genes may be involved in specifying the differences between
proximal (trachea and main bronchi) and distal (lung bud) mesenchyme.
