Hox5 Genes Regulate the Wnt2/2b-Bmp4-Signaling Axis during Lung Development.

Hox genes are required for proper anteroposterior axial patterning and the development of several organ systems. Here, we show that all three Hox5 paralogous genes play redundant roles in the developing lung. Hoxa5;Hoxb5;Hoxc5 triple-mutant embryos develop severely hypoplastic lungs with reduced branching and proximal-distal patterning defects.

Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb.

To date, only the five most posterior groups of Hox genes, Hox9-Hox13, have demonstrated loss-of-function roles in limb patterning. Individual paralog groups control proximodistal patterning of the limb skeletal elements. Hox9 genes also initiate the onset of Hand2 expression in the posterior forelimb compartment, and collectively, the posterior HoxA/D genes maintain posterior Sonic Hedgehog (Shh) expression.