Scylla and charybdis: two novel negative regulators of growth. J. Reiling , E. Hafen. Zoological Institute, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.

   Growth in Drosophiladepends on the activity of the insulin receptor (Inr) signaling pathway. Mutations in positive components of this signaling cascade (DInr, chico, PI3K, PKB/dAkt, PDK1, e. g.) give rise to small flies that are developmentally delayed but show no pattern malformations. The size reduction is brought about by a decrease in both cell number and cell size. On the other hand, a hypomorphic mutation in PTEN(phosphatase and tensin homolog on chromosome 10), the only known bona fidenegative regulator of the DInr pathway, generates bigger flies.
   In order to identify novel genes affecting growth, we performed an EP (enhancer/promoter) screen using a novel double-headed EP element. Among the candidate lines, we identified two EP insertions in the scyllalocus that suppressed the effect of PKB (protein kinase B)/PDK1 (3’- phosphoinositide-dependent kinase-1) co-overexpression in the eye. By BLASTP search we found a highly homologous Drosophilaprotein, designated charybdis. Recently, the mammalian scylla/charybdishomolog has been identified and been shown to be a transcriptional target of HIF-1, a master regulator of oxygen homeostasis in mammals. This finding raises the intriguing possibility of a cross-talk between growth processes and oxygen sensing. A description of scylla-/charybdis-overexpression phenotypes as well as a characterization of loss-of-function mutants will be presented.