Distinct Hox protein sequences determine specificity in different tissues

Hox genes encode evolutionarily conserved transcription factors that contro l the morphological diversification along the anteroposterior (A/P) body ax is. Expressed in precise locations in the ectoderm, mesoderm, and endoderm, Hox proteins have distinct regulatory activities in different tissues. How Hox proteins achieve tissue-specific functions and why cells lying at equi valent A/P positions but in different germ layers have distinctive response s to the same Hox protein remains to be determined. Here, we examine this q uestion by identifying parts of Hox proteins necessary for Hox function in different tissues. Available genetic markers allow the regulatory effects o f two Hox proteins, Abdominal-A (AbdA) and Ultrabithorax (Ubx), to be disti nguished in the Drosophila embryonic epidermis and visceral mesoderm (VM), Chimeric Ubx/AbdA proteins were tested in both tissues and used to identify protein sequences that endow AbdA with a different target gene specificity from Ubx. We found that distinct protein sequences define AbdA, as opposed to Ubx, function in the epidermis vs. the VM, These sequences lie mostly o utside the homeodomain (HD), emphasizing the importance of non-HD residues for specific Hox activities. Hox tissue specificity is therefore achieved b y sensing distinct Hox protein structures in different tissues.