GENERATION OF MULTIPLE ANTAGONISTIC DOMAINS ALONG THE PROXIMODISTAL AXIS DURING DROSOPHILA LEG DEVELOPMENT

homothorax (hth) is a Drosophila member of the Meis family of homeobox genes. hth function is required for the nuclear localization of the H ox cofactor Extradenticle (ESD). We show here that there is also a pos ttranscriptional control of HTH by exd: exd activity is required for t he apparent stability of the HTH protein. In leg imaginal discs, hth e xpression is limited to the domain of exd function and this domain is complementary to the domain in which the Wingless (WC;) and Decapentap legic (DPP) signals are active. We demonstrate that WG and DPP act tog ether through their targets Distal-less (Dll) and dachshund (dac) to r estrict hth expression, and therefore EXD's nuclear localization, to t he most proximal regions of the leg disc, Furthermore, there is a reci procal repression exerted by HTH on these and other DPP and WG downstr eam targets that restricts their expression to non-hth-expressing cell s. Thus, there exists in the leg disc a set of mutually antagonistic i nteractions between proximal cells, which we define as those that expr ess hth, and distal cells, or those that do not express hth. In additi on, we show that dac negatively regulates Dll, We suggest that these a ntagonistic relationships help to convert the WG and DPP activity grad ients into discreet domains of gene expression along the proximodistal axis.