COORDINATE REGULATION OF DOWNSTREAM GENES BY EXTRADENTICLE AND THE HOMEOTIC SELECTOR PROTEINS

Mutations in the Drosophila gene extradenticle (exd), a homologue of t he human proto-oncogene pbx1, cause homeotic transformations by alteri ng the morphological consequences of homeotic selector gene activity. exd has been proposed to act by contributing to the specificity of sel ector homeodomain proteins for their downstream targets. Here we show that exd is indeed required for the appropriate regulation of at least some of these target genes. Expression patterns of wingless, teashirt and decapentaplegic (dpp) are altered in the embryonic midgut of embr yos lacking exd, while the expression of their respective regulators ( abd-A, Antp and Ubx) remains normal. Co-regulation of dpp by exd and U bx was investigated in greater detail by examining the expression of r eporter constructs in exd embryos. These experiments not only define d pp regulatory regions responsive to exd, but also distinguish two func tions of exd in the regulation of dpp. exd acts with Ubx to activate d pp expression in parasegment 7 (PS7), via a minimal visceral mesoderm enhancer, and exd represses dpp expression anterior to PS7. We show th at even when Ubx is ubiquitously expressed at high levels in exd embry os, Ubx is incapable of activating dpp enhancer expression. Thus, exd is an indispensable component in target gene regulation by the homeoti c selector proteins.