HOMEOBOX GENES FROM CLUSTER-A AND CLUSTER-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 morphogenet ic interactions between the epithelium and its mesenchyme. In order to better understand the molecular mechanisms regulating these interacti ons in time and space, the expression patterns of Hox genes isolated e xclusively from the branching region of the developing lung have been investigated. Reverse transcriptase PCR identified Hoxa-1, Hoxa-3, Hox a-5, Hoxb-3, Hoxb-4, Hoxb-6, Hoxb-7, and Hoxb-8 transcripts from withi n this tissue at 11.5 day post coitum (E11.5). Northern blot, in situ hybridization and PCR analyses demonstrated qualitative and quantitati ve differences in expression patterns for each gene assessed in this r egion thus providing evidence for Hox gene temporal colinearity. Furth ermore, although not within the context of strict anteroposterior defi nition, Hox genes located within a more 5' region in both clusters wer e found to have greater spatial expression constrictions when compared to their more 3' counterparts. These Hox genes were also differential ly expressed both between and within specific germ cell lineage deriva tives. Such patterns of expression suggest that Hoxgenes play a role i n the specification and maturation of lung cell lineage derivatives th roughout the pseudoglandular, canalicular and terminal sac phases of l ung development.