Activation of knot (kn) specifies the 3-4 intervein region in the Drosophila wing

Hedgehog (Hh) plays an important role in Drosophila ming patterning by indu cing expression of Dpp, which serves to organize the wing globally across t he A-P axis. We show here how Hh signalling also plays a direct role in pat terning the medial wing through the activation of the Hh-target gene, knot (kn), kil is expressed in Hh-responsive cells near the A-P compartment boun dary, where its expression is dependent on fit, a component of Hh signallin g. kn is required for the proper positioning of veins 3 and 4 and to preven t ectopic venation between them. Furthermore, the expansion anteriorly of t he normal kn expression domain causes an associated anterior shift in the p osition of vein 3 in the resultant wing. Ectopic expression of kn elsewhere in the wing imaginal disc results in the failure to properly activate the vein initiation genes, rho and Dl. Expression of the gene encoding the EGF- receptor (EGFR), which is required for vein initiation and subsequent diffe rentiation, is normally depressed in the 3-4 intervein region. This downreg ulation of EGFR in the medial portion of the imaginal disc is dependent on kn activity and ectopic expression of kn inactivates EGFR elsewhere in the wing primordium. We propose kn expression in Hh-responsive cells of the win g blade anlagen during the late third instar creates a zone of cells in the medial wing in which vein primordia cannot be induced. The primordia for v eins 3 and 4 are laid down adjacent to the kn-imposed vein-free zone, presu mably by a signalling factor (such as Vn) also synthesized in the medial re gion of the wing.