Hox genes are best known for their role in axial patterning during embryogenesis, but they have also been implicated in the development and patterning of cutaneous accessory organs, such as hair follicles and mammary glands. How do they function in this context? Here, by showing that Hoxc8 can initiate an ectopic mammary gland programme in mice, Lara Carroll and Mario Capecchi propose that Hox genes regulate the distribution of cutaneous appendages (p. ). They first show that Hoxc8 is transiently expressed in the early surface ectoderm prior to mammary line formation. The researchers then show that the conditional overexpression of Hoxc8 – to express it in regions where it is not normally expressed – results in the formation of ectopic mammary placodes. These ectopic rudiments express known mammary placode markers, such as Tbx3 and Wnt10b. The authors further report that the ablation of ectodermal Tbx3 prevents the formation of both normal and ectopic mammary rudiments, suggesting that Tbx3 is directly regulated by Hoxc8 during mammary development. Together, these and other findings highlight a role for Hoxc8 in the initial stages of mammary development and suggest that Hoxc8 and other Hox genes play roles during the regional specification of cutaneous appendages.
