Drosophila null slimb clones transiently deregulate Hedgehog-independent transcription of wingless in all limb discs, and induce decapentaplegic transcription linked to imaginal disc regeneration.

Drosophila Slimb (Slmb) is a F-box/WD40 protein which potentially participates in the ubiquitin proteolysis machinery. During development, Slmb is required in limb discs to repress Hedgehog (Hh) target genes, i.e. wingless (wg) and decapentaplegic (dpp), as well as the Wg signal transduction pathway. These repression functions have been proposed from studies using weak slmb alleles. Interestingly, experiments with strong slmb alleles have revealed additional mechanisms in which slmb is required, such as leg dorsal-ventral restriction. We have isolated new alleles of the slmb gene in a screen for new negative regulators of dpp: several amorphs (characterized by genetic and molecular criteria) and a cold-sensitive hypomorph. By performing somatic clone experiments with these new amorphic slmb alleles, we have determined that regulation of Dpp and Wg morphogens by Slmb could be different from what has already been published. We show here that in leg discs, lack of slmb function derepresses the transcription of wg independently of Hh signaling. We present evidence that ectopic legs resulting from slmb(-) clone induction only come from wg misexpression in the normal dpp domain, as ectopic proximo-distal axis are induced dorsally, and adult ectopic legs are often perfect with respect to antero-posterior polarity. In wing discs, transcription of wg, which is normally independent of Hh signaling, is also derepressed in the absence of slmb function. We also describe, in discs bearing amorphic slmb clones and in discs of two other slmb(-) contexts, a novel pattern of dpp expression consisting of an enlargement of the normal dpp domain. Strong evidence indicates that this dpp modification can be linked to imaginal disc regeneration following slmb(-) cell elimination. We have investigated the fate of slmb(-) clones, which disappear before adulthood, and found that two mechanisms of cell elimination can account for imaginal cell regeneration: an early apoptosis and a mechanism of sorting-out which excludes all slmb(-) clones from all imaginal discs. This result suggests that Slmb is likely to be involved, in addition to its repression role on Dpp and Wg, in some other essential cellular mechanism, as in the absence of Slmb, cell affinities are dramatically modified regardless of the deregulated morphogen and of the type of imaginal disc.