Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs

The Fused (Fu) serine-threonine kinase and the Suppressor of fused (Su(fu)) product are parr of the Hedgehog (Hh) signalling pathway both in embryos a nd in imaginal discs. In wing imaginal discs, the Hh signal induces Cubitus interruptus (Ci) accumulation and activates patched (ptc) and decapentaple gic (dpp) expression along the anterior/posterior (A/P) boundary. In this p aper, we have examined the role of the Fu and Su(fu) proteins in the regula tion of Hh target gene expression in wing imaginal discs, by using differen t classes of fu alleles and an amorphic Su(fu) mutation. We show that, at t he A/P boundary, Fu kinase activity is involved in the maintenance of high pre expression and in the induction of late anterior engrailed (en) express ion. These combined effects can account for the modulation of Ci accumulati on and for the precise localization of the Dpp morphogen stripe. In contras t, in more anterior cells which do not receive Hh signal, we show that Fu p lays a role independent of its kinase function in the regulation of Ci accu mulation. In these cells, Fu may be involved in the stabilization of a larg e protein complex which is probably responsible for the regulation of Ci cl eavage and/or targeting to nucleus. We propose that the Fused function is n ecessary for the activation of full-length Ci and counteracts the negative Su(fu) effect on the pathway, leading to en, ptc and dpp expression. (C) 19 98 Elsevier Science Ireland Ltd. All rights reserved.