Homeobox genes from clusters A and B demonstrate characteristics of temporal colinearity and differential restrictions in spatial expression domains in the branching mouse lung.

Lung branching morphogenesis is accomplished by reciprocal morphogenetic interactions between the epithelium and its mesenchyme. In order to better understand the molecular mechanisms regulating these interactions in time and space, the expression patterns of Hox genes isolated exclusively from the branching region of the developing lung have been investigated. Reverse transcriptase PCR identified Hoxa-1, Hoxa-3, Hoxa-5, Hoxb-3, Hoxb-4, Hoxb-6, Hoxb-7, and Hoxb-8 transcripts from within this tissue at 11.5 day post coitum (E11.5). Northern blot, in situ hybridization and PCR analyses demonstrated qualitative and quantitative differences in expression patterns for each gene assessed in this region thus providing evidence for Hox gene temporal colinearity. Furthermore, although not within the context of strict anteroposterior definition, Hox genes located within a more 5' region in both clusters were found to have greater spatial expression constrictions when compared to their more 3' counterparts. These Hox genes were also differentially expressed both between and within specific germ cell lineage derivatives. Such patterns of expression suggest that Hox genes play a role in the specification and maturation of lung cell lineage derivatives throughout the pseudoglandular, canalicular and terminal sac phases of lung development.